DRUG INTERACTION BETWEEN SIMVASTATIN AND ITRACONAZOLE IN MALE AND FEMALE RATS
|
|
- Winfred Allen
- 6 years ago
- Views:
Transcription
1 /01/ $3.00 DRUG METABOLISM AND DISPOSITION Vol. 29, No. 7 Copyright 2001 by The American Society for Pharmacology and Experimental Therapeutics 331/ DMD 29: , 2001 Printed in U.S.A. DRUG INTERACTION BETWEEN SIMVASTATIN AND ITRACONAZOLE IN MALE AND FEMALE RATS MICHI ISHIGAMI, KIYOSHI KAWABATA, WATARU TAKASAKI, TOSHIHIKO IKEDA, TORU KOMAI, KIYOMI ITO, AND YUICHI SUGIYAMA Drug Metabolism and Pharmacokinetics Research Laboratories, New Drug Development Division and Product Strategy Department, Sankyo Co., Ltd., Shinagawa-ku, Tokyo, Japan (M.I., K.K., W.T., T.I., T.K.); School of Pharmaceutical Sciences, Kitasato University, Minato-ku, Tokyo, Japan (K.I.); and Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo, Japan (Y.S.) (Received January 2, 2001; accepted April 10, 2001) This paper is available online at ABSTRACT: Taking into account the species and sex differences in drug interactions based on the inhibition of cytochrome P450 (P450)- mediated drug metabolism, we examined whether the interaction between simvastatin and itraconazole observed in humans could also occur in rats, the most commonly used animal species for pharmacokinetic studies. Itraconazole inhibited the in vitro metabolism of simvastatin in female rat liver microsomes, but not in male rat liver microsomes. Using anti-p450 antisera, the main P450 isozyme responsible for the metabolism of simvastatin was identified as CYP3A in female rats and CYP2C11 in male rats. Therefore, the sex difference in the inhibition of simvastatin metabolism by itraconazole seems to be caused by a difference in the P450 isozymes responsible for the metabolism Drug interactions can be classified into two types: in one case the pharmacological effects or side-effects of drugs are altered by concomitantly administered drugs, and in the other case the effects and sideeffects of the concomitantly administered drugs are altered by the original drugs. In both cases, the drug interactions have been evaluated based on changes in plasma drug levels in clinical situations. In the case of HMG-CoA 1 reductase inhibitors, it has been reported in clinical situations that plasma levels of simvastatin and lovastatin, which are in their prodrug lactone forms, were increased more than 10-fold by the concomitantly administered antifungal agent, itraconazole (Neuvonen and Jalava, 1996; Neuvonen et al., 1998). Itraconazole is known as a potent inhibitor of CYP3A4, one of the major cytochrome P450 (P450) isozymes in humans (Olkkola et al., 1994; Varhe et al., 1994). We have investigated the causes of the increase in the plasma levels of the prodrug-type lactone forms of HMG-CoA reductase inhibitors by concomitantly administered itraconazole. We used a pharmacokinetic model (Ito et al., 1998a,b) involving the pharmacokinetic parameters for itraconazole and the K i values obtained in in vitro studies using human 1 Abbreviations used are: HMG-CoA, 3-hydroxy-3-methylglutaryl-coenzyme A; V 0, initial formation rate; HPLC, high-performance liquid chromatography; TLC, thin-layer chromatography; CMC, carboxymethylcellulose; AUC, area under the curve. Address correspondence to: Yuichi Sugiyama, Professor, Graduate School of Pharmaceutical Sciences, University of Tokyo, 3-1,7-Chome, Hongo, Bunkyoku, Tokyo , Japan. sugiyama@mol.f.u-tokyo.ac.jp 1068 of simvastatin in male and female rats and the different ability of itraconazole to inhibit CYP3A and CYP2C11. In addition, the effect of itraconazole on the pharmacokinetics of simvastatin in rats was also investigated. The area under the curve value of simvastatin was increased approximately 1.6-fold by the concomitant use of itraconazole (50 mg/kg) in female rats, whereas in male rats, itraconazole had no effect. In conclusion, it was found that the results obtained in male rats did not reflect the results in humans as far as the inhibition of simvastatin metabolism by itraconazole was concerned. The P450 isozymes involved in the metabolism of drugs should be taken into consideration when rats are used as a model animal for humans in the investigation of drug interactions. liver microsomes. The predicted increase in plasma simvastatin levels by the concomitant use of itraconazole agreed reasonably well with those observed in clinical situations (Ishigami et al., 2001). In the case of drugs at the development stage, in vivo drug interaction studies have been sometimes conducted with experimental animals because it is difficult to conduct such studies at this stage in humans (Damanhouri et al., 1988; Ikeda et al., 1988). It has become possible, to a certain extent, to predict the possibility of in vivo drug interactions in humans from results obtained in in vitro systems using human liver microsomes. For the scale-up of human metabolism from in vitro to in vivo, some information about the drug concentration in liver is required; however, the measurement is usually impossible. In experimental animals administered with the drug, the concentrations in liver can be easily measured, and the information can be referred to for prediction of in vivo drug interaction in human from in vitro metabolism. For the prediction to be more accurate, it is necessary to choose an appropriate animal as a model. However, there is a possibility that the results obtained in experimental animals do not reflect the drug interactions in humans because of species (Nelson et al., 1996; Eagling et al., 1998) and sex differences (Kato and Kamataki, 1982; Kamataki et al., 1983) in P450 isozymes. Accordingly, taking into account the species and sex differences in the drug interactions based on the inhibition of P450 activities, we have investigated whether a drug interaction in humans actually occurs in rats, the most commonly used animal species in pharmacokinetic studies. In vitro and in vivo inhibition studies were conducted
2 SEX-DEPENDENT INHIBITION OF SIMVASTATIN METABOLISM IN RATS 1069 in male and female rats to investigate the effect of itraconazole, a specific inhibitor of CYP3A4 in humans, on simvastatin metabolism, and the results obtained were compared with the drug interaction observed in humans. Materials and Methods Chemicals and Reagents. 14 C-Labeled simvastatin (lactone form), simvastatin (lactone form), and simvastatin acid (Na salt) used in the present study were synthesized at Sankyo Co., Ltd. (Tokyo, Japan). Rat liver microsomes were prepared from male and female Sprague-Dawley rats (Japan SLC, Hamamatsu, Japan) according to conventional methods. Anti-rat P450 antisera preparations (anti-rat CYP2C11 prepared from goat and anti-rat CYP3A2 prepared from rabbit) were purchased from Daiichi Pure Chemicals Co., Ltd. (Tokyo, Japan). All other chemicals and reagents used were commercially available and of guaranteed purity. In Vitro Metabolism of Simvastatin. After preincubation of 0.2 ml of rat liver microsome (0.2 mg of protein/ml) containing an NADPH-generating system (2.5 mm NADP, 25 mm glucose 6-phosphate, 2 units of glucose-6- phosphate dehydrogenase, and 10 mm MgCl 2 ) at 37 C for 3 min, an ethanol solution of [ 14 C]simvastatin was added. After a 10-min incubation at 37 C, the reaction was stopped by adding 0.4 ml of ethanol and vortex mixing. The mixture was centrifuged at 10,000 rpm for 3 min, and the quantity of metabolites in the supernatant was analyzed by HPLC or TLC. The HPLC conditions were as follows: column, C 8 ET250/4 Nucleosil 100-5; mobile phase (linear gradient), acetonitrile/0.05% phosphoric acid 35:75 (0 min) 3 75:35 (25 min); and flow rate, 1 ml/min. The HPLC eluate was collected at intervals of 30 s, and a certain volume of scintillation cocktail (Pico-Fluor, Packard Instrument Co., Meriden, CT) was added to each eluate. The radioactivity was then counted in a liquid scintillation counter (2250 CA, Packard). The TLC analysis of simvastatin and its metabolites was performed under the following TLC conditions: silica-gel plates, 0.25 mm thickness, 60 F 254 (Merck KgaA, Darmstadt, Germany); and development solvent system, toluene/acetone/acetic acid (50:50:0.5, v/v/v). The amount of unchanged drug and its metabolites was determined by radioluminography using BAS 2000 equipment (Fuji Photo Film Co., Tokyo, Japan). To identify the P450 isozymes responsible for the metabolism of simvastatin, an inhibition study using anti-rat P450 antisera was performed. Anti-rat P450 antisera or corresponding control sera ( mg of IgG) were added to rat liver microsomes (pooled for five male rats or five female rats, 10 mg of protein/ml, 10 l), and the resulting mixture was preincubated at room temperature for 30 min. Then, in the same manner as described above, NADPHgenerating system was added and preincubated for 3 min at 37 C. Subsequently, an ethanol solution of [ 14 C]simvastatin was added to each microsomal preparation to give a final concentration of 20 M and then incubated for 5 min at 37 C (0.2 mg of protein/ml, total volume of 0.5 ml). The reaction was stopped by addition of 1 ml of methanol, and the quantity of metabolites in the supernatant was determined by TLC. Inhibition of Simvastatin Metabolism by Itraconazole. Itraconazole (dimethylacetamide solution; final concentrations: 0 20 M) and simvastatin (ethanol solution; final concentration: 20 M) were added to male or female rat liver microsomal preparations (0.2 mg of protein/ml). After incubation for 10 min at 37 C, the amount of simvastatin metabolites formed was determined in the same manner as described above. We calculated K i values from Dixon plots by concurrent fitting of the data to the following equation using the WinNonlin program: 1/V 0 1 K m /S /V max I K m / K i S V max (1) where V 0 is the initial rate of metabolism, K m is the Michaelis-Menten constant, V max is the maximum rate of metabolism, and S and I indicate the concentration of the substrate (simvastatin) and the inhibitor (itraconazole), respectively. In Vivo Interaction Study. [ 14 C]Simvastatin suspended in 0.5% carboxymethylcellulose (CMC) solution was administered orally to fasted male and female rats at a dose of 10 mg/kg immediately after oral administration of itraconazole suspended in 0.5% CMC solution at a dose of 50 mg/kg or 0.5% CMC solution. Blood samples (0.3 ml each) were taken from the jugular vein of each rat using heparinized syringes at various time points after the administration of [ 14 C]simvastatin. Immediately after sampling, the plasma was separated by centrifuging the blood sample at 10,000 rpm for 3 min under refrigerated conditions. Then a 50- l aliquot of each plasma sample was transferred to a glass vial and solubilized by mixing with 0.1 ml of tissue solubilizer (NCS-II, Amersham Pharmacia Biotech, Inc. (Piscataway, NJ). Subsequently, a liquid scintillation cocktail (Hionic Fluor, Packard) was added to each solubilized sample, and the radioactivity was counted in a liquid scintillation counter (2250 CA, Packard). For quantification of the metabolites, 200 l of acetonitrile was added to 100 l of each plasma sample, and after centrifugation of the mixture at 10,000 rpm for 3 min, the supernatant was collected. Furthermore, the metabolites remaining in the precipitate were re-extracted with a mixture of acetonitrile/water (3:1, v/v), and the supernatant obtained was combined with the supernatant collected above and evaporated to dryness under the stream of N 2 gas. The residue was dissolved in acetonitrile/ water (3:1, v/v), and the metabolites were separated by TLC and quantified by liquid scintillation counting. The AUC values (0 6 h or 0 8 h) were calculated by the trapezoidal method. Results Characteristics of Simvastatin Metabolism in Rat Liver Microsomes. During the incubation of simvastatin with female rat liver microsomes, metabolites M-1 (6 -hydroxy simvastatin), M-2 (3,5 dihydrodiol simvastatin), and simvastatin acid were formed as the main metabolites, which were identical to those observed in human liver microsomes, although their relative amounts differed. On the other hand, in male rat liver microsomes, metabolite M-3, which was not detected in human and female rat liver microsomes, and simvastatin acid were detected as main metabolites (Fig. 1). The formation of M-1 and M-2, the main metabolites in female rat liver microsomes, was inhibited by about 80 and 50%, respectively, by the addition of 0.25 mg of IgG anti-cyp3a2 antiserum, while the formation of these metabolites was scarcely affected by the addition of anti-cyp2c11 antiserum (Fig. 2, a and b). These results suggest that the P450 isozyme responsible for the metabolism of simvastatin to M-1 and M-2 in female rats is CYP3A. On the other hand, the formation of M-3, the main metabolite in male rat liver microsomes, was inhibited by about 90% by the addition of 0.25 mg of IgG anti-cyp2c11 antiserum, but not by the addition of anti-cyp3a2 antiserum (Fig. 2c). These findings suggest that the P450 isozyme responsible for the metabolism of simvastatin to M-3 in male rats is CYP2C11. Effect of Itraconazole on the Formation of Simvastatin Metabolites (M-1, M-2, and M-3) in Rat Liver Microsomes. The metabolism of simvastatin in female rat liver microsomes was inhibited FIG. 1.HPLC chromatograms of [ 14 C]simvastatin metabolites produced by human liver microsomes and rat liver microsomes. [ 14 C]simvastatin (20 M) was incubated at 37 C for 30 min with human liver microsomes (0.2 mg/ml) or rat liver microsomes (0.2 mg/ml) in the presence of an NADPH-generating system.
3 1070 ISHIGAMI ET AL. FIG. 2.Effects of anti-p450 sera on the formation of M-1(a), M-2(b), and M-3(c) from simvastatin in female and male rat liver microsomes. Pooled rat liver microsomes (five female or five male rats, 0.1 mg of protein/10 l) were preincubated for 30 min at room temperature with 0.05 to 0.25 mg of IgG of anti-rat P450 sera or control sera, preincubated for 3 min at 37 C with NADPH-generating system, and then incubated with simvastatin (20 M) at 37 C for 10 min. Results (mean S.E.) were based on triplicate determinations. a, female; b, female; c, male., anti-cyp3a2;, anti-cyp2c11. by itraconazole in a concentration-dependent manner (Fig. 3a), whereas the formation of M-3 in male rat liver microsomes was scarcely inhibited by itraconazole (Fig. 3b). The inhibition of simvastatin metabolism by itraconazole was kinetically analyzed with Dixon plots of the data obtained from female rat liver microsomes. As a result, the inhibition of the formation of M-1 (Fig. 4a) and M-2 (Fig. 4b) by itraconazole was demonstrated to be competitive. In addition, the K i values for the inhibition of the formation of M-1 and M-2 by itraconazole were calculated to be and 1.22 M, respectively. Effect of Concomitantly Administered Itraconazole on the Pharmacokinetics of Simvastatin in Male and Female Rats. Figure 6 shows the time courses of the plasma concentration of simvastatin after oral administration of simvastatin (10 mg/kg), with or without concomitant oral administration of itraconazole (50 mg/ kg) to male and female rats. The AUC and C max values and the degree of increase in these parameters produced by itraconazole are summarized in Table 2. The AUC and C max values of the unchanged drug after oral administration of simvastatin to female rats was increased about 1.6- and 2.0-fold, respectively, by the concomitant administration of itraconazole (Fig. 5a; Table 1). However, the plasma concentration of the unchanged drug after an oral administration of simvastatin to male rats was not affected by the concomitant administration of itraconazole (Fig. 5b, Table 1). Discussion Simvastatin is metabolized mainly by CYP3A4 in humans (Vickers et al., 1990; Prueksaritanont et al., 1997). In rats, a sex difference in the pharmacokinetics of simvastatin has been reported (Ohtawa and Uchiyama, 1992); however, the P450 isozyme(s) responsible for simvastatin metabolism have not been identified. In the present study, the main simvastatin metabolites formed by male and female rat liver microsomes were found to be different, and the main metabolites in female rat liver microsomes, M-1 (6 -hydroxy simvastatin) and M-2 (3,5 -dihydrodiol simvastatin), were found to be identical to the main metabolites in human liver microsomes following comparison of their HPLC retention times and TLC R f (ratio at flow) values (Ishigami et al., 2001) (Fig. 1). In contrast, the main metabolite in male rat liver microsomes, M-3, was shown not to correspond to any of the metabolites FIG. 3.Inhibition of the formation of simvastatin metabolites, M-1, M-2, and M-3, by itraconazole in female (a) and male (b) rat liver microsomes. Simvastatin (20 M) was incubated at 37 C for 10 min with pooled rat liver microsomes (five male or five female rats, 0.2 mg of protein/ml) in the absence or presence of itraconazole ( M). Control activities were obtained in the absence of itraconazole. Results (mean S.E.) were based on triplicate determinations., M-1;, M-2; F, M-3.
4 SEX-DEPENDENT INHIBITION OF SIMVASTATIN METABOLISM IN RATS 1071 FIG. 4.Dixon plots for the inhibition of the formation of simvastatin metabolites, M-1 (a) and M-2 (b), by itraconazole in female rat liver microsomes. Simvastatin (5 50 M) was incubated at 37 C for 10 min with pooled female rat liver microsomes (five female rats, 0.2 mg of protein/ml) in the absence or presence of itraconazole ( M). Results (mean S.E.) were based on triplicate determinations. E, 5 M simvastatin;, 10 M;, 20 M; Œ, 50 M. V 0, M-1 or M-2 formation rate (nmol/min/mg). FIG. 5.Influence of itraconazole on plasma concentrations of simvastatin in female (a) and male (b) rats. Itraconazole was administrated orally at a dose of 50 mg/kg, and then simvastatin was administrated orally at a dose of 10 mg/kg 1 min later. Each point represents the mean S.D. (n 3)., plasma concentration of simvastatin alone;, plasma concentration of simvastatin in the presence of itraconazole. TABLE 1 Pharmacokinetic parameters of simvastatin in the absence or presence of itraconazole AUC AUC ( I) AUC ( I) /AUC C max C max( I) C max( I) /C max ng h/ml ng/ml Female Male formed in human liver microsomes. The chemical structure of M-3 was proposed to be 3 -hydroxy simvastatin based on the structure of the main metabolite formed in male rat liver microsomes already identified (Ohtawa and Uchiyama, 1992). From the inhibition study with anti-rat P450 antisera, the P450 isozyme responsible for simvastatin metabolism in male rats was demonstrated to be different from that in female rats. In the formation of M-3 by male rat liver microsomes, CYP2C11 was suggested to play the main role, while the CYP3A family was mainly responsible in the formation of M-1 and M-2 in female rat liver microsomes (Fig. 2). Furthermore, itraconazole inhibited the metabolism of simvastatin in female rats but not in male rats (Fig. 4). Considering the previous finding that itraconazole inhibited the metabolism mediated by CYP3A2 in male rats (Yamano et al., 1999), the sex difference in the inhibition by itraconazole was suggested to be attributable to a difference in the ability of itraconazole to inhibit CYP2C11 and CYP3A activity. In addition, the metabolism of simvastatin in human liver microsomes was also inhibited by itraconazole, indicating that female rats rather than male rats reflect the in vitro inhibition in humans. In the investigation of the effect of concomitantly administered itraconazole on the pharmacokinetics of simvastatin in rats, the in vitro metabolism of simvastatin was not inhibited by itraconazole in male rats. In female rats in which inhibition of the in vitro metabolism of simvastatin was observed, the AUC of simvastatin was increased, although the degree of increase was significantly lower than that observed in clinical situations (more than 10-fold) (Neuvonen et al., 1998). As seen in Fig. 1, the amount of M-1 and M-2 formed relative to the acid form
5 1072 ISHIGAMI ET AL. was less in female rat liver microsomes than in human liver microsomes. Because the formation of M-1 and M-2 is more susceptible to inhibition by itraconazole than that of the acid form, the difference in the formation ratio of metabolites in female rats and humans might be one of the causes for the smaller inhibitory effect of the concomitantly administered itraconazole in female rats, compared with that observed in humans. The drug interaction based on the inhibition of simvastatin metabolism mediated by CYP3A4 in humans could not be reproduced in the study with male rats. On the other hand, in the study with female rats, a drug interaction was observed, although the degree of increase in the AUC of simvastatin was smaller in rats than in humans. These results suggest that female rats are a more appropriate animal model than their male counterparts for the investigation of the drug interaction based on the inhibition of simvastatin metabolism mediated by CYP3A4. Since species and sex differences are observed in P450 isozymes, the establishment of appropriate experimental conditions, taking into account the P450 isozymes responsible for drug metabolism, should be confirmed as far as drug interaction studies using rats as a model animal for humans are concerned. References Damanhouri Z, Gumbleton M, Nicholls PJ and Shaw MA (1988) In vivo effects of itraconazole on hepatic mixed function oxidase. J Antimicrob Chemother 21: Eagling VA, Tjia JF and Back DJ (1998) Differential selectivity of cytochrome P450 inhibitors against probe substrates in human and rat liver microsomes. Br J Clin Pharmacol 45: Ikeda T, Mori I, Komai T and Tanaka M (1988) Interaction of cimetidine and ranitidine, the H2-receptor blockers, with mexazolam, a benzodiazepinooxazole- anxiolytic in rats. Xenobio Metab Dispos 3: Ishigami M, Uchiyama M, Kondo T, Iwabuchi H, Inoue S, Takasaki W, Ikeda T, Komai T, Ito K and Sugiyama Y (2001) Inhibition of in vitro metabolism of simvastatin by itraconazole in humans and prediction of in vivo drug-drug interactions. Pharmacol Res, in press. Ito K, Iwatsubo T, Kanamitsu S, Nakajima Y and Sugiyama Y (1998a) Quantitative prediction of in vivo drug clearance and drug interactions from in vitro data on metabolism, together with binding and transport. Annu Rev Pharmacol Toxicol 38: Ito K, Iwatsubo T, Kanamitsu S, Ueda K, Suzuki H and Sugiyama Y (1998b) Prediction of pharmacokinetic alterations caused by drug-drug interactions: metabolic interaction in the liver. Pharmacol Rev 50: Kamataki T, Maeada K, Yamazoe Y, Nagai T and Kato R (1983) Sex difference of cytochrome P-450 in the rat: purification, characterization, and quantification of constitutive forms of cytochrome P-450 from liver microsomes of male and female rats. Arch Biochem Biophys 225: Kato R and Kamataki T (1982) Cytochrome P-450 as a determinant of sex difference of drug metabolism in the rat. Xenobiotica 12: Nelson DR, Koymans L, Kamataki T, Stegeman JJ, Feyereisen R, Waxman DJ, Waterman MR, Gotoh O, Coon MJ, Estabrook RW, et al. (1996) P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 6:1 42. Neuvonen PJ and Jalava KM (1996) Itraconazole drastically increases plasma concentrations of lovastatin and lovastatin acid. Clin Pharmacol Ther 60: Neuvonen PJ, Kantola T and Kivisto KT (1998) Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole. Clin Pharmacol Ther 63: Ohtawa M and Uchiyama N (1992) Sex difference in metabolism of simvastatin by rat hepatic microsomes. Eur J Drug Metab Pharmacokinet 17: Olkkola KT, Backman JT and Neuvonen PJ (1994) Midazolam should be avoided in patients receiving the systemic antimycotics ketoconazole or itraconazole. Clin Pharmacol Ther 55: Prueksaritanont T, Gorham LM, Ma B, Liu L, Yu X, Zhao JJ, Slaughter DE, Arison BH and Vyas KP (1997) In vitro metabolism of simvastatin in humans [SBT] identification of metabolizing enzymes and effect of the drug on hepatic P450s. Drug Metab Dispos 25: Varhe A, Olkkola KT and Neuvonen PK (1994) Oral triazolam is potentially hazardous to patients receiving systemic antimycotics ketoconazole or itraconazole. Clin Pharmacol Ther 56: Vickers S, Duncan CA, Vyas KP, Kari PH, Arison B, Prakash SR, Ramjit HG, Pitzenberger SM, Stokker G and Duggan DE (1990) In vitro and in vivo biotransformation of simvastatin, an inhibitor of HMG-CoA reductase. Drug Metab Dispos 18: Yamano K, Yamamoto K, Kotaki H, Sawada Y and Iga T (1999) Quantitative prediction of metabolic inhibition of midazolam by itraconazole and ketoconazole in rats: implication of concentrative uptake of inhibitors into liver. Drug Metab Dispos 27:
Different effects of itraconazole on the pharmacokinetics of fluvastatin and lovastatin
Different effects of itraconazole on the pharmacokinetics of fluvastatin and lovastatin K. T. Kivistö, T. Kantola & P. J. Neuvonen Department of Clinical Pharmacology, University of Helsinki and Helsinki
More informationEffects of grapefruit juice on pharmacokinetics of atorvastatin and pravastatin in Japanese
et al. British Journal of Clinical Pharmacology DOI:.46/j.365-5.3.3.x Effects of grapefruit juice on pharmacokinetics of atorvastatin and pravastatin in Japanese Ichiro Fukazawa, Naoki Uchida, Eiji Uchida
More informationLack of effect of ketoconazole on the pharmacokinetics of rosuvastatin in healthy subjects
Blackwell Science, LtdOxford, UKBCPBritish Journal of Clinical Pharmacology0306-5251Blackwell Publishing 200254Original ArticleCo-administration of rosuvastatin and ketoconazolek. J. Cooper Lack of effect
More informationPDF hosted at the Radboud Repository of the Radboud University Nijmegen
PDF hosted at the Radboud Repository of the Radboud University Nijmegen This full text is a publisher's version. For additional information about this publication click this link. http://hdl.handle.net/2066/14779
More informationWithdrawal of Cerivastatin Revealed a Flaw of Post-marketing Surveillance System in the United States
Bull. Natl. Inst. Health Sci., 123 Notes # Withdrawal of Cerivastatin Revealed a Flaw of Post-marketing Surveillance System in the United States Journal of American Medical Association (JAMA) Statin HMG
More informationInternational Journal of Pharma and Bio Sciences DETERMINATION OF SIMVASTATIN IN HUMAN PLASMA USING LIQUID CHRMATOGRAPHY-MASS SPECTROMETRY ABSTRACT
Research Article Nanotechnology International Journal of Pharma and Bio Sciences ISSN 0975-6299 DETERMINATION OF SIMVASTATIN IN HUMAN PLASMA USING LIQUID CHRMATOGRAPHY-MASS SPECTROMETRY KHALED. M. ALAKHALI
More informationQuantification of lovastatin in human plasma by LC/ESI/MS/MS using the Agilent 6410 Triple Quadrupole LC/MS system
Quantification of lovastatin in human plasma by LC/ESI/MS/MS using the Agilent 641 Triple Quadrupole LC/MS system Application Note Clinical Research Author Siji Joseph Agilent Technologies Bangalore, India
More informationEffect of voriconazole on the pharmacokinetics and pharmacodynamics of zolpidem in healthy subjects
British Journal of Clinical Pharmacology DOI:1.1111/j.1365-21.26.277.x Effect of voriconazole on the pharmacokinetics and pharmacodynamics of zolpidem in healthy subjects Teijo I. Saari, Kari Laine, Kari
More informationA Bioequivalence Study of an Albendazole Oral Suspension Produced in Iran and a Reference Product in Sheep
A Bioequivalence Study of an Albendazole Oral Suspension Produced in Iran and a Reference Product in Sheep Ali Eslami, DVM, PhD 1 Ali Rassouli, DVM, PhD 2 Behnam Meshki, DVM, PhD 1 Gholam Reza Shams, BSc
More informationReceived May 30, 2007; accepted August 15, 2007
0090-9556/07/3511-1990 1995$20.00 DRUG METABOLISM AND DISPOSITION Vol. 35, No. 11 Copyright 2007 by The American Society for Pharmacology and Experimental Therapeutics 16816/3267964 DMD 35:1990 1995, 2007
More informationGlutaredoxin Is Involved in the Formation of the Pharmacologically Active Metabolite of Clopidogrel from Its GSH Conjugate
1521-009X/12/4009-1854 1859$25.00 DRUG METABOLISM AND DISPOSITION Vol. 40, No. 9 Copyright 2012 by The American Society for Pharmacology and Experimental Therapeutics 45914/3792147 DMD 40:1854 1859, 2012
More informationTitle Revision n date
A. THIN LAYER CHROMATOGRAPHIC TECHNIQUE (TLC) 1. SCOPE The method describes the identification of hydrocortisone acetate, dexamethasone, betamethasone, betamethasone 17-valerate and triamcinolone acetonide
More informationDevelopment and Validation of HPLC-UV Method for Simultaneous Determination of Nevirapine, 2-OH Nevirapine and 3-OH Nevirapine in Human Plasma.
International Journal of PharmTech Research CODEN (USA): IJPRIF ISSN : 0974-4304 Vol.6, No.1, pp 49-57, Jan-March 2014 Development and Validation of HPLC-UV Method for Simultaneous Determination of Nevirapine,
More information(Received April 8, 1998; accepted July 30, 1998) This paper is available online at ABSTRACT:
0090-9556/99/2702-0173 179$02.00/0 DRUG METABOLISM AND DISPOSITION Vol. 27, No. 2 Copyright 1999 by The American Society for Pharmacology and Experimental Therapeutics Printed in U.S.A. COMPARISON OF CYTOCHROME
More informationINVOLVEMENT OF CYP2E1 AS A LOW-AFFINITY ENZYME IN PHENACETIN O-DEETHYLATION IN HUMAN LIVER MICROSOMES
0090-9556/99/2708-0860 865$02.00/0 DRUG METABOLISM AND DISPOSITION Vol. 27, No. 8 Copyright 1999 by The American Society for Pharmacology and Experimental Therapeutics Printed in U.S.A. INVOLVEMENT OF
More informationDetermination of β2-agonists in Pork Using Agilent SampliQ SCX Solid-Phase Extraction Cartridges and Liquid Chromatography-Tandem Mass Spectrometry
Determination of β2-agonists in Pork Using Agilent SampliQ SCX Solid-Phase Extraction Cartridges and Liquid Chromatography-Tandem Mass Spectrometry Application Note Food Safety Authors Chenhao Zhai Agilent
More informationSorafenib (free base, >99%) was obtained from Chemie Tek (Indianapolis, IN), and
Supplemental Methods Chemicals and Reagents Sorafenib (free base, >99%) was obtained from Chemie Tek (Indianapolis, IN), and isotopically-labeled 13 C- 2 H 3 -sorafenib (labeled atoms on N-methyl position)
More informationYoshihisa Shitara, Masaru Hirano, Hitoshi Sato, and Yuichi Sugiyama
0022-3565/04/3111-228 236$20.00 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 311, No. 1 Copyright 2004 by The American Society for Pharmacology and Experimental Therapeutics 68536/1171497
More informationEFFECT OF MULTIPLE DOSING OF KETOCONAZOLE ON PHARMACOKINETICS OF MIDAZOLAM, A CYTOCHROME P-450 3A SUBSTRATE IN BEAGLE DOGS
0090-9556/02/3001-63 68$3.00 DRUG METABOLISM AND DISPOSITION Vol. 30, No. 1 Copyright 2002 by The American Society for Pharmacology and Experimental Therapeutics 357/953757 DMD 30:63 68, 2002 Printed in
More informationGLUCURONIDATION OF STATINS IN ANIMALS AND HUMANS: A NOVEL MECHANISM OF STATIN LACTONIZATION
0090-9556/02/3005-505 512$7.00 DRUG METABOLISM AND DISPOSITION Vol. 30, No. 5 Copyright 2002 by The American Society for Pharmacology and Experimental Therapeutics 623/975196 DMD 30:505 512, 2002 Printed
More informationDetermination of 6-Chloropicolinic Acid (6-CPA) in Crops by Liquid Chromatography with Tandem Mass Spectrometry Detection. EPL-BAS Method No.
Page 1 of 10 Determination of 6-Chloropicolinic Acid (6-CPA) in Crops by Liquid Chromatography with Tandem Mass Spectrometry Detection EPL-BAS Method No. 205G881B Method Summary: Residues of 6-CPA are
More informationPrediction of Species Differences (Rats, Dogs, Humans) in the In Vivo Metabolic Clearance of YM796 by the Liver from In Vitro Data
0022-3565/97/2832-0462$03.00/0 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 283, No. 2 Copyright 1997 by The American Society for Pharmacology and Experimental Therapeutics Printed in
More informationProstaglandin E2 ELISA Kit - Monoclonal
Prostaglandin E2 ELISA Kit - Monoclonal Cat. No.:DEIA4977 Pkg.Size:96T/480T General Description Prostaglandin E2 (PGE2) is a primary product of arachidonic acid metabolism in many cells. Like most eicosanoids,
More informationInfluence of fluvoxamine on carvedilol metabolism and plasma disposition in vitro and in vivo experiments
Influence of fluvoxamine on carvedilol metabolism and plasma disposition in vitro and in vivo experiments MARIA BIANCA ABRUDAN* 1, DANA MARIA MUNTEAN 1, DANIELA SAVETA POPA 2, LAURIAN VLASE 1, ANA-MARIA
More informationProstaglandin E Metabolites ELISA KIT
Prostaglandin E Metabolites ELISA KIT Cat. No.:DEIA6216 Pkg.Size:96T Intended use Prostaglandin E Metabolites ELISA is for the quantitative determination of Prostaglandin E Metabolite in urine, whole blood,
More informationA mong the 20 leading prescription
Safety and Statins: Pharmacologic and Clinical Perspectives Michael B. Bottorff, PharmD A mong the 20 leading prescription drugs in the United States, 3 agents atorvastatin (Lipitor), simvastatin (Zocor),
More informationPilot experiments to investigate the glucuronidation of axitinib with human liver microsomes.
Zientek MA, Goosen TC, Tseng E, Lin J, Bauman JN, Walker GS, Kang P, Jiang Y, Freiwald S, Neul D and Smith BJ. In Vitro Kinetic Characterization of Axitinib Metabolism. Drug Metab Dispos. Supplemental
More informationTHIN LAYER CHROMATOGRAPHY
THIN LAYER CHROMATOGRAPHY Thin layer chromatography is the best known technique of plant biochemistry. TLC is used for preliminary separation and determination of plant constituents. It is helpful for
More informationSupporting Information
Notes Bull. Korean Chem. Soc. 2013, Vol. 34, No. 1 1 http://dx.doi.org/10.5012/bkcs.2013.34.1.xxx Supporting Information Chemical Constituents of Ficus drupacea Leaves and their α-glucosidase Inhibitory
More informationMetabolism and metabolic inhibition of cilnidipine in human liver microsomes 1
263 2003, Acta Pharmacologica Sinica Chinese Pharmacological Society Shanghai Institute of Materia Medica Chinese Academy of Sciences http://www.chinaphar.com Metabolism and metabolic inhibition of cilnidipine
More informationDevelopment of a Cell-penetrating Peptide that Exhibits Responsive. Changes in its Secondary Structure in the Cellular Environment
Development of a Cell-penetrating Peptide that Exhibits Responsive Changes in its Secondary Structure in the Cellular Environment iroko Yamashita, 1 Takuma Kato, 2 Makoto ba, 2 Takashi Misawa, 1 Takayuki
More informationTCP Transl Clin Pharmacol
TCP 2017;25(1):10-14 http://dx.doi.org/10.12793/tcp.2017.25.1.10 Comparative pharmacokinetic and tolerability evaluation of two simvastatin 20 mg formulations in healthy Korean male volunteers Seol Ju
More informationSPE-LC-MS/MS Method for the Determination of Nicotine, Cotinine, and Trans-3-hydroxycotinine in Urine
SPE-LC-MS/MS Method for the Determination of Nicotine, Cotinine, and Trans-3-hydroxycotinine in Urine J. Jones, Thermo Fisher Scientific, Runcorn, Cheshire, UK Application Note 709 Key Words SPE, SOLA
More informationIn vivo and In vitro Drug Interactions Study of Glimepride with Atorvastatin and Rosuvastatin
Pharmacy Practice In vivo and In vitro Drug Interactions Study of Glimepride with Atorvastatin and Rosuvastatin Galani VJ 1, Vyas M 1 Department of Pharmacology, A. R. College of Pharmacy and G. H. Patel
More informationDetermination and pharmacokinetics of manidipine in human plasma by HPLC/ESIMS
BIOMEDICAL CHROMATOGRAPHY Biomed. Chromatogr. 21: 836 840 (2007) Published 836 online ORIGINAL 12 April RESEARCH 2007 in Wiley InterScience ORIGINAL RESEARCH (www.interscience.wiley.com).827 Determination
More informationIN VITRO IDENTIFICATION OF THE HUMAN CYTOCHROME P450 ENZYMES INVOLVED IN THE METABOLISM OF R( )- AND S( )-CARVEDILOL
0090-9556/97/2508-0970 977$02.00/0 DRUG METABOLISM AND DISPOSITION Vol. 25, No. 8 Copyright 1997 by The American Society for Pharmacology and Experimental Therapeutics Printed in U.S.A. IN VITRO IDENTIFICATION
More informationThe Third Department of Internal Medicine, University of Tokyo Faculty of Medicine, Hongo, Tokyo 113
Endocrinol. Japon. 1974, 21 (2), 115 ` 119 A Radioimmunoassay for Serum Dehydroepiandrosterone HISAHIKO SEKIHARA, TOHRU YAMAJI, NAKAAKI OHSAWA AND HIROSHI IBAYASHI * The Third Department of Internal Medicine,
More informationMetabolic Mechanism of Delamanid, a New Anti-Tuberculosis Drug, in Human Plasma
Metabolic Mechanism of Delamanid, a New Anti-Tuberculosis Drug, in Human Plasma 2015 年 下川義彦 Table of Contents List of Abbreviations Chapter 1 General Introduction 1 Chapter 2 In Vivo Pharmacokinetics and
More informationItraconazole and Clarithromycin as Ketoconazole Alternatives for Clinical CYP3A Inhibition Studies to Quantify Victim DDI Potential
Itraconazole and Clarithromycin as Ketoconazole Alternatives for Clinical CYP3A Inhibition Studies to Quantify Victim DDI Potential Alice Ban Ke, Ph.D. Consultant & Scientific Advisor Simcyp Limited Alice.Ke@certara.com
More informationMouse C-peptide EIA. Cat. No. YII-YK013-EX FOR LABORATORY USE ONLY
Mouse C-peptide EIA Cat. No. YII-YK013-EX FOR LABORATORY USE ONLY TOYO 2CHOME, KOTO-KU, TOKYO, 135-0016, JAPAN http://www.cosmobio.co.jp e-mail : export@cosmobio.co.jp Phone : +81-3-5632-9617 FAX : +81-3-5632-9618
More informationPREDICTION OF THE IN VIVO INTERACTION BETWEEN MIDAZOLAM AND MACROLIDES BASED ON IN VITRO STUDIES USING HUMAN LIVER MICROSOMES
0090-9556/03/3107-945 954$7.00 DRUG METABOLISM AND DISPOSITION Vol. 31, No. 7 Copyright 2003 by The American Society for Pharmacology and Experimental Therapeutics 924/1072492 DMD 31:945 954, 2003 Printed
More informationHPLC-UV Determination of Abacavir Sulphate in Pharmaceutical Dosage Forms
Asian Journal of Chemistry Vol. 19, No. 5 (2007), 3412-3416 HPLC-UV Determination of Abacavir Sulphate in Pharmaceutical Dosage Forms A. SHANTA KUMARI*, K. PRAKASH, K.E.V. NAGOJI and M.E.B. RAO Department
More informationAMIODARONE and DESETHYLAMIODARONE IN PLASMA BY UV FAST CODE Z33610
AMIODARONE and DESETHYLAMIODARONE IN PLASMA BY UV FAST CODE Z33610 INTRODUCTION Amiodarone is an antiarrhythmic agent used for various types of tachyarrhythmias, both ventricular and supraventricular arrhythmias.
More informationPHARMACOKINETIC STUDY OF DEXTROMETHORPHAN WITH URINARY EXCRETION
PHARMACOKINETIC STUDY OF DEXTROMETHORPHAN WITH URINARY EXCRETION Heesun CHUNG, Wonkyung YANG, Hwakyung CHOI, Wontack JIN, Sihnyoung SIHN, Youngchan YOO National Institute of Scientific Investigation, Seoul,
More informationEffect of a Selenium Analogue of [L Title Transport of Candida pelliculosa (C Dedicated to Professor Masaya Okano Retirement) Author(s) Shimizu, Eiichi; Yamana, Ryutaro; T Kenji Citation Bulletin of the
More informationChuang Lu, Suresh K. Balani, Mark G. Qian, Shimoga R. Prakash, Patricia S. Ducray, and Lisa L. von Moltke
0022-3565/10/3322-562 568$20.00 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 332, No. 2 Copyright 2010 by The American Society for Pharmacology and Experimental Therapeutics 161893/3550697
More informationEffect of fluconazole dose on the extent of fluconazole-triazolam interaction
Br J Clin Pharmacol 1996; 42: 465 47 Effect of fluconazole dose on the extent of fluconazole-triazolam interaction ANU VARHE, KLAUS T. OLKKOLA & PERTTI J. NEUVONEN Department of Clinical Pharmacology,
More informationMitoCheck Complex II Activity Assay Kit
MitoCheck Complex II Activity Assay Kit Item No. 700940 www.caymanchem.com Customer Service 800.364.9897 Technical Support 888.526.5351 1180 E. Ellsworth Rd Ann Arbor, MI USA TABLE OF CONTENTS GENERAL
More informationDetermination of Clarithromycin in Human Plasma by LC-EI Tandem Mass Spectrometry: Application to Bioequivalence Study
Determination of Clarithromycin in Human Plasma by LC-EI Tandem Mass Spectrometry: Application to Bioequivalence Study Syed N Alvi, Ph.D Clinical Studies & Empirical Ethics Department King Faisal Specialist
More informationDienes Derivatization MaxSpec Kit
Dienes Derivatization MaxSpec Kit Item No. 601510 www.caymanchem.com Customer Service 800.364.9897 Technical Support 888.526.5351 1180 E. Ellsworth Rd Ann Arbor, MI USA TABLE OF CONTENTS GENERAL INFORMATION
More informationHuman Obestatin ELISA
K-ASSAY Human Obestatin ELISA For the quantitative determination of obestatin in human serum and plasma Cat. No. KT-495 For Research Use Only. 1 Rev. 081309 K-ASSAY PRODUCT INFORMATION Human Obestatin
More informationCHAPTER 8 HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC) ANALYSIS OF PHYTOCHEMICAL CONSTITUENTS OF M. ROXBURGHIANUS AND P. FRATERNUS PLANT EXTRACTS
CHAPTER 8 HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC) ANALYSIS OF PHYTOCHEMICAL CONSTITUENTS OF M. ROXBURGHIANUS AND P. FRATERNUS PLANT EXTRACTS CHAPTER 8: HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC)
More informationComprehensive Study of SLE as a Sample. Preparation Tool for Bioanalysis
Comprehensive Study of SLE as a Sample Preparation Tool for Bioanalysis Wan Wang, Warren Chen, Jerry Wang Bonna-Agela Technologies 179 Southern Street, West TEDA, Tianjin, China Abstract A simple, fast,
More informationMetabolism of 1 - and 4-Hydroxymidazolam by Glucuronide Conjugation Is Largely Mediated by UDP-Glucuronosyltransferases 1A4, 2B4, and 2B7
0090-9556/10/3811-2007 2013$20.00 DRUG METABOLISM AND DISPOSITION Vol. 38, No. 11 Copyright 2010 by The American Society for Pharmacology and Experimental Therapeutics 35295/3635725 DMD 38:2007 2013, 2010
More informationInternational Journal of Pharmaceutical Sciences and Drug Research 2018; 10(1): 46-50
Available online at www.ijpsdr.com International Journal of Pharmaceutical Sciences and Drug Research 2018; 10(1): 46-50 Research Article ISSN: 0975-248X CODEN (USA): IJPSPP Pharmacokinetic Drug - Drug
More informationQUANTITATIVE PREDICTION OF THE INTERACTION OF MIDAZOLAM AND HISTAMINE H 2 RECEPTOR ANTAGONISTS IN RATS
0090-9556/98/2604-0318 323$02.00/0 DRUG METABOLISM AND DISPOSITION Vol. 26, No. 4 Copyright 1998 by The American Society for Pharmacology and Experimental Therapeutics Printed in U.S.A. QUANTITATIVE PREDICTION
More informationValidation of Quantitative Method for Glycidol Fatty Acid Esters (GEs) in Edible Oils
102nd AOCS Annual Meeting & Expo Validation of Quantitative Method for Glycidol Fatty Acid Esters (GEs) in Edible Oils Hiroki Shiro, Naoki Kondo and Yoshinori Masukawa * Tochigi Research Labs Kao corporation
More informationDetermination of Aflatoxins in Food by LC/MS/MS. Application. Authors. Abstract. Experimental. Introduction. Food Safety
Determination of Aflatoxins in Food by LC/MS/MS Application Food Safety Authors Masahiko Takino Agilent Technologies 9-1 Takakura-Cho Hachiouji-Shi, Tokyo Japan Toshitsugu Tanaka Kobe Institute of Health
More informationDIRECT EXTRACTION OF BENZODIAZEPINE METABOLITE WITH SUPERCRITICAL FLUID FROM WHOLE BLOOD
DIRECT EXTRACTION OF BENZODIAZEPINE METABOLITE WITH SUPERCRITICAL FLUID FROM WHOLE BLOOD Kenichi TAKAICHI, Shuji SAITOH, Yoshio KUMOOKA, Noriko TSUNODA National Research Institute of Police Science, Chiba,
More informationHPLC Analysis of Sugars
HPLC Analysis of Sugars Pre-Lab Exercise: 1) Read about HPLC, sugars and the experiment and its background. 2) Prepare a flowchart as appropriate for the lab exercise. 3) Note the various sugar concentrations
More informationIn vitro metabolism of montelukast by Cytochrome P450s (CYPs) and UDPglucuronosyltransferases
In vitro metabolism of montelukast by Cytochrome P450s (CYPs) and UDPglucuronosyltransferases (UGTs) Josiane de Oliveira Cardoso, Regina Vincenzi Oliveira, Jessica Bo Li Lu Zeruesenay Desta Department
More informationAnalysis of Amino Acids Derived Online Using an Agilent AdvanceBio AAA Column
Application Note Pharmaceutical and Food Testing Analysis of Amino Acids Derived Online Using an Agilent AdvanceBio AAA Column Author Lu Yufei Agilent Technologies, Inc. Abstract A liquid chromatographic
More informationEffect of rifampicin on the pharmacokinetics and pharmacodynamics of glimepiride
Effect of rifampicin on the pharmacokinetics and pharmacodynamics of glimepiride Mikko Niemi, Kari T. KivistoÈ, Janne T. Backman & Pertti J. Neuvonen Department of Clinical Pharmacology, University of
More informationIdentification & Confirmation of Structurally Related Degradation Products of Simvastatin
Identification & Confirmation of Structurally Related Degradation Products of Simvastatin Power of QTRAP Systems for Identification and Confirmation of Degradation Products Dilip Reddy 1, Chandra Sekar
More informationXTreme 200 Human Liver Microsomes Lot No Human Liver Microsomes Pool of 200 (100 Male and 100 Female) Suspension medium: 250 mm sucrose
XTreme 200 Human Liver Microsomes Lot No. 1710084 Human Liver Microsomes Pool of 200 (100 Male and 100 Female) Suspension medium: 250 mm sucrose H2610 0.5 ml at 20 mg/ml H2620 1.0 ml at 20 mg/ml H2630
More informationAnalytical Method for 2, 4, 5-T (Targeted to Agricultural, Animal and Fishery Products)
Analytical Method for 2, 4, 5-T (Targeted to Agricultural, Animal and Fishery Products) The target compound to be determined is 2, 4, 5-T. 1. Instrument Liquid Chromatograph-tandem mass spectrometer (LC-MS/MS)
More informationKey words: Collagen synthesis - N-Terminal peptide of type III procollagen - Tumor marker - Liver cancer - Liver cirrhosis
[Gann, 75, 130-135; February, 1984] HIGH CONCENTRATIONS OF N-TERMINAL PEPTIDE OF TYPE III PROCOLLAGEN IN THE SERA OF PATIENTS WITH VARIOUS CANCERS, WITH SPECIAL REFERENCE TO LIVER CANCER Terumasa HATAHARA,
More informationPelagia Research Library
Available online at www.pelagiaresearchlibrary.com Der Pharmacia Sinica, 2015, 6(1):6-10 ISSN: 0976-8688 CODEN (USA): PSHIBD Validated RP-HPLC method for simultaneous estimation of metformin hydrochloride
More informationFluvoxamine impairs single-dose caffeine clearance without altering caffeine pharmacodynamics
British Journal of Clinical Pharmacology DOI:10.1111/j.1365-2125.2005.02467.x Fluvoxamine impairs single-dose caffeine clearance without altering caffeine pharmacodynamics Kerry E. Culm-Merdek, Lisa L.
More informationEASIMIP TM PATULIN Product Code: P250 / P250B
EASIMIP TM PATULIN Product Code: P250 / P250B Molecularly imprinted polymer columns for use in conjunction with HPLC. For in vitro use only. P250B/V5/03.09.18 www.r-biopharm.com Contents Page Test Principle...
More informationVOLKER FISCHER, LAURIE JOHANSON, FRANCIS HEITZ, ROBERT TULLMAN, ELIZABETH GRAHAM, JEAN-PIERRE BALDECK AND WILLIAM T. ROBINSON
0090-9556/99/2703-0410 416$02.00/0 DRUG METABOLISM AND DISPOSITION Vol. 27, No. 3 Copyright 1999 by The American Society for Pharmacology and Experimental Therapeutics Printed in U.S.A. THE 3-HYDROXY-3-METHYLGLUTARYL
More informationThiol-Activated gem-dithiols: A New Class of Controllable. Hydrogen Sulfide (H 2 S) Donors
Thiol-Activated gem-dithiols: A New Class of Controllable Hydrogen Sulfide (H 2 S) Donors Yu Zhao, Jianming Kang, Chung-Min Park, Powell E. Bagdon, Bo Peng, and Ming Xian * Department of Chemistry, Washington
More informationApplication Note. Author. Abstract. Introduction. Food Safety
Determination of β2-agonists in Pork with SPE eanup and LC-MS/MS Detection Using Agilent BondElut PCX Solid-Phase Extraction Cartridges, Agilent Poroshell 120 column and Liquid Chromatography-Tandem Mass
More informationDevelopment, Optimization and Validation of HPLC Method for Determination of Pravastatin Sodium in Tablets
INTERNATIONAL JOURNAL OF ADVANCES IN PHARMACY, BIOLOGY AND CHEMISTRY Research Article Development, Optimization and Validation of HPLC Method for Determination of Pravastatin Sodium in Tablets Vania Maslarska*
More informationPelagia Research Library
Available online at www.pelagiaresearchlibrary.com Der Pharmacia Sinica, 2014, 5(5):91-98 ISSN: 0976-8688 CODEN (USA): PSHIBD A novel RP-HPLC method development and validation of Perindopril Erbumine in
More informationDetermination of propranolol in dog plasma by HPLC method
Asian Journal of Pharmacodynamics and Pharmacokinetics Paper ID 1608-2281-2008-08020153-06 Copyright by Hong Kong Medical Publisher Received December 30, 2007 ISSN 1608-2281 2008; 8(2):153-158 Accepted
More informationIN VITRO BIOTRANSFORMATION OF SILDENAFIL (VIAGRA): IDENTIFICATION OF HUMAN CYTOCHROMES AND POTENTIAL DRUG INTERACTIONS
0090-9556/00/2804-0392 397$02.00/0 DRUG METABOLISM AND DISPOSITION Vol. 28, No. 4 Copyright 2000 by The American Society for Pharmacology and Experimental Therapeutics Printed in U.S.A. IN VITRO BIOTRANSFORMATION
More informationDifferent Effects of SLCO1B1 Polymorphism on the Pharmacokinetics of Atorvastatin and Rosuvastatin
nature publishing group Different Effects of SLCO1B1 Polymorphism on the Pharmacokinetics of Atorvastatin and Rosuvastatin MK Pasanen 1, H Fredrikson 1, PJ Neuvonen 1 and M Niemi 1 Thirty-two healthy volunteers
More informationCytochrome P450 enzymes are involved in the metabolism of foreign substances
KHAN, MOHAMMAD MAZAMAL, M.S. Inhibition of Cytochrome P450 2E1 and Cytochrome P450 2A6 by Essential Oils: Tarragon (Artemisia dracunculus) and Basil (Ocimum basilicum). (2014) Directed by Dr. Gregory M.
More informationEffect of grapefruit juice on the disposition of manidipine enantiomers in healthy subjects
DOI:10.1111/j.1365-2125.2006.02583.x British Journal of Clinical Pharmacology Effect of grapefruit juice on the disposition of manidipine enantiomers in healthy subjects Tsukasa Uno, 1,3 Tadashi Ohkubo,
More informationA HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC ASSAY FOR LERCANIDIPINE HYDROCHLORIDE
Int. J. Chem. Sci.: 6(1), 2008, 441-446 A HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC ASSAY FOR LERCANIDIPINE HYDROCHLORIDE S. APPALA RAJU, ARVIND B. KARADI and SHOBHA MANJUNATH HKES s College of Pharmacy,
More informationRebaudioside a From Multiple Gene Donors Expressed in Yarrowia Lipolytica
Residue Monograph prepared by the meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), 82 nd meeting 2016 Rebaudioside a From Multiple Gene Donors Expressed in Yarrowia Lipolytica This
More informationEXPERIMENT 13: Isolation and Characterization of Erythrocyte
EXPERIMENT 13: Isolation and Characterization of Erythrocyte Day 1: Isolation of Erythrocyte Steps 1 through 6 of the Switzer & Garrity protocol (pages 220-221) have been performed by the TA. We will be
More informationA Validated Chiral Liquid Chromatographic Method for The Enantiomeric Separation of Dapoxetine Hydrochloride
Received on 15/05/2012; Revised on 22/05/2012; Accepted on 09/06/2012 A Validated Chiral Liquid Chromatographic thod for The Enantiomeric Separation of Dapoxetine Hydrochloride T.Rohith 1 and S. Ananda
More informationRat C-Peptide EIA. Cat. No. YII-YK010-EX FOR LABORATORY USE ONLY
Rat C-Peptide EIA Cat. No. YII-YK010-EX FOR LABORATORY USE ONLY TOYO 2CHOME, KOTO-KU, TOKYO, 135-0016, JAPAN http://www.cosmobio.co.jp e-mail : export@cosmobio.co.jp 1 Phone : +81-3-5632-9617 FAX : +81-3-5632-9618
More informationab HMG-CoA Reductase Activity Assay Kit (Colorimetric)
ab204701 HMG-CoA Reductase Activity Assay Kit (Colorimetric) Instructions for Use For rapid, sensitive and accurate detection of HMG-CoA Reductase Activity. This product is for research use only and is
More informationLC-MS/MS Method for the Determination of Tenofovir from Plasma
LC-MS/MS Method for the Determination of Tenofovir from Plasma Kimberly Phipps, Thermo Fisher Scientific, Runcorn, Cheshire, UK Application Note 687 Key Words SPE, SOLA CX, Hypersil GOLD, tenofovir Abstract
More informationUSP purity analysis of pravastatin sodium using the Agilent 1120 Compact LC
USP purity analysis of pravastatin sodium using the Agilent 1120 Compact LC Application Note Manufacturing QA/QC Authors Syed S. Lateef, Siji Joseph Agilent Technologies Bangalore, India 500 400 Pravastatin
More informationQuantitative Method to measure Glycidol Fatty Acid Esters (GEs) in Edible Oils
101 st AOCS Annual Meeting & Expo Quantitative Method to measure Glycidol Fatty Acid Esters (GEs) in Edible Oils Hiroki Shiro* 1, Yoshinori Masukawa 1, Naoki Kondo 1 and Naoto Kudo 2 1 Tochigi Research
More informationPharmacokinetic and pharmacodynamic interactions between phenprocoumon and atenolol or metoprolol
Br. J. clin. Pharmac. (1984), 17, 97S-12S Pharmacokinetic and pharmacodynamic interactions between phenprocoumon and atenolol or metoprolol H. SPAHN', W. KIRCH2,. MUTSCHLR',.. OHNHAUS2, N. R. KITFRINGHAM2,
More informationJuly 2007 Biol. Pharm. Bull. 30(7) (2007)
July 2007 Biol. Pharm. Bull. 30(7) 1237 1241 (2007) 1237 Prediction of a 1 -Adrenoceptor Occupancy in the Human Prostate from Plasma Concentrations of Silodosin, Tamsulosin and Terazosin to Treat Urinary
More informationAnalysis of L- and D-Amino Acids Using UPLC Yuta Mutaguchi 1 and Toshihisa Ohshima 2*
Analysis of L- and D-Amino Acids Using UPLC Yuta Mutaguchi 1 and Toshihisa Ohshima 2* 1 Department of Biotechnology, Akita Prefectural University, Akita City, Japan; 2 Department of Biomedical Engineering,
More informationBACKGROUND AND PURPOSE
British Journal of Pharmacology DOI:10.1111/j.1476-5381.010.00913.x www.brjpharmacol.org RESEARCH PAPER Pharmacokinetic interaction between itraconazole and metformin in rats: competitive inhibition of
More informationThe metabolism of 1 - and 4-hydroxymidazolam by glucuronide conjugation is. largely mediated by UDP-glucuronosyltransferases 1A4, 2B4, and 2B7
DMD Fast This article Forward. has not Published been copyedited on and August formatted. 16, The 2010 final version as doi:10.1124/dmd.110.035295 may differ from this version. The metabolism of 1 - and
More informationResearch and Reviews: Journal of Pharmacy and Pharmaceutical Sciences
Research and Reviews: Journal of Pharmacy and Pharmaceutical Sciences A Validated Spectrophotometric Method for Determination of Paliperidone Palmitate in Bulk Drug and its Pharmaceutical Dosage Form.
More informationUnit I (b) Paper Chromatography
Unit I (b) Paper Chromatography Presentation by Mr. VELLURU REDDY MOHAN Assistant Professor Department of Pharmaceutical Analysis Krishna Teja Pharmacy college Subject : PHARMACEUTICAL ANALYSIS- II (15R00602)
More informationScreening of Antihistamine Agents (Diphenhydramine) with Blood and Urine Samples by REMEDi-HS System
Screening of Antihistamine Agents (Diphenhydramine) with Blood and Urine Samples by REMEDi-HS System Ohtsuji M, Ohshima T, Takayasu T, Nishigami J, Kondo T, Lin Z, Minamino T Department of Legal Medicine,
More informationDEVELOPMENT AND VALIDATION OF HPLC METHOD FOR QUANTIFICATION OF CEFOTAXIME IN PLASMA OF PATANWADI SHEEP
Explor Anim Exploratory Med Res, Animal and Medical Research, ISSN Vol.5, 2277- Issue 470X 2, (Print), December, ISSN 2319-247X 2015 (Online) Vol.5, Issue - 2, 2015, p. 190-195 Website: www.animalmedicalresearch.org
More informationAnalysis of Acrylamide in French Fries using Agilent Bond Elut QuEChERS AOAC kit and LC/MS/MS
Analysis of Acrylamide in French Fries using Agilent Bond Elut QuEChERS AOAC kit and LC/MS/MS Food Application Author Fadwa Al-Taher Institute for Food Safety and Health Illinois Institute of Technology
More information