Exploiting BDDCS and the Role of Transporters
|
|
- Brian Long
- 6 years ago
- Views:
Transcription
1 Exploiting BDDCS and the Role of Transporters (Therapeutic benefit of scientific knowledge of biological transporters, understanding the clinical relevant effects of active transport on oral drug absorption) Leslie Z. Benet, Ph.D. Department of Bioengineering and Therapeutics Sciences University of California, San Francisco SARI 2014 Pharmaceutical Science, Medicine Registration and Control Pretoria March 11, 2014
2 Now following Dr. Shah s excellent presentation, all delegates are well aware of BCS, the criteria involved and its use in obtaining biowaivers. In the early 2000s, I listened attentively to many presentations such as that given by Dr. Shah and began to recognize that certain previously unrecognized drug disposition characteristics may be inherent in the BCS system.
3 Wu and Benet recognized that for drugs exhibiting high intestinal permeability rates the major route of elimination in humans was via metabolism, while drugs exhibiting poor intestinal permeability rates were primarily eliminated in humans as unchanged drug in the urine and bile. Therefore they suggested that at least for drugs on the market, where extent of metabolism is always known, but extent of absorption may not have been quantitated, that metabolism may serve as a surrogate for permeability rate, and as an additional parameter for supporting a biowaiver of in vivo bioequivalence studies.
4 Major Routes of Drug Elimination High Solubility Low Solubility High Permeability Rate Low Permeability Rate Class 1 Metabolism Class 3 Renal & Biliary Elimination of Unchanged Drug Class 2 Metabolism Class 4 Renal & Biliary Elimination of Unchanged Drug
5 Biopharmaceutics Drug Disposition Classification System BDDCS High Solubility Low Solubility Extensive Metabolism Class 1 High Solubility Extensive Metabolism (Rapid Dissolution and 70% Metabolism for Biowaiver) Class 2 Low Solubility Extensive Metabolism Poor Metabolism Class 3 High Solubility Poor Metabolism Class 4 Low Solubility Poor Metabolism Wu and Benet, Pharm. Res. 22: (2005)
6 Major Differences Between BDDCS and BCS Purpose: BCS Biowaivers of in vivo bioequivalence studies. BDDCS Prediction of drug disposition and potential DDIs in the intestine & liver. BDDCS Predictions based on intestinal permeability rate BCS Biowaivers based on extent of absorption, which in a number of cases does not correlate with jejunal permeability rates
7 What are the Implications for New Molecular Entities and DDIs? For an NME, measuring a surrogate of human intestinal absorption, such as Caco-2 permeability or even PAMPA, allows prediction of the major route of elimination in humans prior to dosing either to animals or man. Furthermore, one knows whether DDIs relating to metabolism will be a major factor or not.
8 The recognition of the correlation between intestinal permeability rate and extent of metabolism allows prediction of BDDCS class for an NME to be based on passive membrane permeability. Our recent work suggests that even measurements in nonviable membranes like PAMPA will give the correct prediction.
9 2013 publications from the Benet Lab concerning permeability measurement correlations and intestinal transporters The Role of BCS (Biopharmaceutics Classification System) and BDDCS (Biopharmaceutics Drug Disposition Classification System) in Drug Development. L. Z. Benet. J. Pharm. Sci. 102, (2013) Drug Discovery and Regulatory Considerations for Improving In Silico and In Vitro Predictions that Use Caco-2 as a Surrogate for Human Intestinal Permeability Measurements. C. A. Larregieu and L. Z. Benet. AAPS J. 15, (2013). Intestinal Drug Transporters: An Overview. M. Estudante, J. G. Morais, G. Soveral and L. Z. Benet. Adv. Drug Deliv. Rev. 65, (2013).
10 The recognition of the correlation between intestinal permeability rate and extent of metabolism and our finding that a nonviable membrane can serve as surrogate marker preceded an explanation for these findings. We suspect that high permeability rate compounds are readily reabsorbed from the kidney lumen and from the bile facilitating multiple access to the metabolic enzymes. This would be particularly important for metabolically eliminated drugs with low hepatic clearance (e.g., diazepam).
11 A major advantage of BDDCS is that for drugs on the market, we know the extent of metabolism and they can generally be correctly classified without expensive and time consuming human permeability studies. I am very pleased that the January 2010 EMA Guideline on the Investigation of Bioequivalence includes metabolism as a criteria for permeability and that EMA only accepts extent of absorption as a criteria for Class 1 biowaivers. Also, the FDA has said informally that they would accept metabolism information. BDDCS gives scientists and clinicians a roadmap for predicting drug disposition and drug-drug interaction characteristics very early, with little additional expense. Let s see further predictions
12 Prediction of Oral Dosing Transporter Effects Based on BDDCS Class High Permeability/ Metabolism Low Permeability/ Metabolism High Solubility Class 1 Transporter effects minimal in gut and liver and clinically insignificant Class 3 Absorptive transporter effects predominate (but can be modulated by efflux transporters) Low Solubility Class 2 Efflux transporter effects predominate in gut, but both uptake & efflux transporters can affect liver Class 4 Absorptive and efflux transporter effects could be important S. Shugarts and L. Z. Benet. Pharm. Res. 26, (2009).
13 Class 1 highly soluble, high permeability, extensively metabolized drugs Transporter effects will be minimal in the intestine and the liver Even compounds like verapamil that can be shown in certain cellular systems (MDR1-MDCK) to be a substrate of P-gp will exhibit no clinically significant P-gp substrate effects in the gut and liver
14 Class 2 poorly soluble, highly permeable, extensively metabolized drugs Efflux transporter effects will be important in the intestine and the liver In the intestine efflux transporter enzyme (CYP 3A4 and UGTs) interplay can markedly affect oral bioavailability In the liver the efflux transporter-enzyme interplay will yield counteractive effects to that seen in the intestine. Uptake transporters can be important for the liver but not the intestine.
15 Intestinal: Transporter Effects High Solubility Low Solubility High Permeability Low Permeability Class 1 Transporter effects minimal Class 3 Absorptive transporter effects predominate (but can be modulated by efflux transporters) Class 2 Efflux transporter effects predominate Class 4 Absorptive and efflux transporter effects could be important
16 P-gp and CYP3A4 Interplay in the Enterocytes Drug not metabolized or transported in the gut Drug metabolized on first entrance Drug cycled 4 times before metabolized Drug metabolites LUMEN Pgp Pgp Pgp Pgp Pgp Pgp 3A4 3A4 3A4 P-gp and CYP3A4 Interplay BLOOD
17 Studies to Characterize Transporter-Enzyme Interplay in CYP3A4 Transfected Caco-2 Cellular Systems Cummins et al., Pharm. Res., 18: (2001) Benet et al., Adv. Drug Deliv. Rev., 50: S3-S11 (2001) Cummins et al., J. Pharmacol. Exp. Ther., 300: (2002) Cummins et al., J. Pharmacol. Exp. Ther., 308: (2004)
18 Oral Dosing Transporter Effects High Permeability/ Metabolism Low Permeability/ Metabolism High Solubility Class 1 Transporter effects minimal in gut and liver Class 3 Absorptive transporter effects predominate (but can be modulated by efflux transporters) Low Solubility Class 2 Efflux transporter effects predominate in gut, but both uptake & efflux transporters can affect liver Class 4 Absorptive and efflux transporter effects could be important
19 Elucidating Rifampin s Inducing and Inhibiting Effects on Glyburide Pharmacokinetics and Blood Glucose in Healthy Volunteers: Unmasking the Differential Effect of Enzyme Induction and Transporter Inhibition for a Drug and Its Primary Metabolite HongXia Zheng, Yong Huang, Lynda Frassetto, and Leslie Z. Benet Clinical Pharmacology & Therapeutics 85:78-85 (2009)
20 Hepatocytes OATP 1B1 = Glyburide M = Glyburide Metabolites Bile 2C9 & 3A Pgp M Bile 2C9 & 3A Bile M M Blood
21 Hepatocytes OATP 1B1 When rifampin is present in the blood it can inhibit OATPs = Glyburide M = Glyburide Metabolites Bile 2C9 & 3A Pgp M Bile 2C9 & 3A Bile M Upon multiple dosing rifampin can induce CYP 2C9 and 3A4 M Blood
22 Study Design Effects of Single IV Rifampin (RIF) on Glyburide Ten Healthy Volunteers Visit 1 Day 1 Glyburide 1.25mg P.O. (PK Study) Visit 2 Day 8 Rifampin 600mg I.V. Glyburide 1.25mg P.O. (PK Study)
23 Study Design (Continued) Inhibition and Induction Effects of RIF on Glyburide ALL Healthy Volunteers Rifampin 600mg P.O. for 6 days Visit 3 Day 15 Rifampin 600mg I.V. Glyburide 1.25mg P.O. (PK study) Visit 4 Day 17 Glyburide 1.25mg P.O. (PK study)
24 Inhibition of Glyburide Uptake by IV RIF Glyburide (ng/ml) Glyburide Control RIF IV+Glyburide Time (h) Cmax 81% T1/2 31% * * AUC0-inf 125% CL/F 53% * * Vss/F 60% * P<0.05 *
25 CYP450 Induction Effect on Glyburide When No RIF Present in the Plasma Glyburide (ng/ml) Glyburide Control Glyburide After RIF Induction Time (h) * * 197% * Cmax 48% AUC0-inf 63% CL/F Vss/F 32% ns
26 Uptake Inhibition and CYP450 Induction Effects on Glyburide When RIF Present in the Plasma Glyburide (ng/ml) Glyburide Control RIF IV+Glyburide After RIF Induction Time (h) * * Cmax 9% AUC0-inf 22% CL/F 37% Vss/F 43% *
27 Caution A simple 4 category system won t predict every interaction. BDDCS doesn t propose that every drug in the class will be substrates or not substrates for uptake and efflux transporters. Rather, BDDCS enumerates what interactions should and should not be investigated.
28 Class 3 highly soluble, low permeability, poorly metabolized drugs Uptake transporters will be important for intestinal absorption and liver entry for these poor permeability drugs However, once these poorly permeable drugs get into the enterocyte or the hepatocyte efflux transporter effects can occur.
29 Recently the FDA has recommended that studies in renal failure patients be carried out even for drugs where renal elimination of unchanged drug is minimal This recommendation comes about in part based on a finding that was related to the development and characterization of BDDCS
30 Studies of Drugs Primarily Eliminated by Metabolism in Renal Failure Patients Potential inhibition or downregulation of metabolic enzymes by uremic toxins could be tested in vitro. We began to recognize that previously unexplained effects of renal disease on hepatic metabolism can result from accumulation of substances (toxins) in renal failure that modify hepatic uptake and efflux transporters. Sun et al., Effect of Uremic Toxins on Hepatic Uptake and Metabolism of Erythromycin. Drug Metab. Dispos. 32: (2004). Sun et al., Hepatic Clearance, But Not Gut Availability, of Erythromycin is Altered in Patients with End-Stage Renal Disease. Clin. Pharmacol. Ther. 87: (2010) Reyes and Benet, Effects of Uremic Toxins on Transport and Metabolism of Different Biopharmaceutics Drug Disposition Classification Systems Xenobiotics. J. Pharm. Sci. 100: (2011)
31 Hepatic Clearance, but Not Gut Availability of Erythromycin Is Altered in Patients with End-Stage Renal Disease Hong Sun, Lynda A. Frassetto, Yong Huang and Leslie Z. Benet Clinical Pharmacology & Therapeutics 87: (2010) Erythromycin is a Class 3 drug that is primarily eliminated unchanged in the bile. It is a substrate for hepatic uptake transporters that we have shown can be inhibited by uremic toxins in end-stage renal disease patients.
32 Erythromycin PK Parameters (mean ± SD) in 12 ESRD patients and12 controls after 125 mg iv and 250 mg oral doses Parameter Healthy Controls ESRD Patients % Change (p value) CL H (L/h/kg) 0.51 ± ± % (p = 0.01) F % 15 ± 6 21 ± 7 36% (NS, p = 0.36) F H % 50 ± ± 15 28% (p = 0.015) F abs F G % 33 ± ± 28
33 Recent Transporter Interplay Reviews from the Benet Lab The Role of Transporters in the Pharmacokinetics of Orally Administered Drugs. S. Shugarts and L. Z. Benet. Pharm. Res. 26, (2009). The Drug Transporter-Metabolism Alliance: Uncovering and Defining the Interplay. L. Z. Benet. Mol. Pharmaceut. 6, (2009). Predicting Drug Disposition via Application of a Biopharmaceutics Drug Disposition Classification System. L. Z. Benet. Basic Clin. Pharmacol. Toxicol. 106, (2010). The Role of BCS (Biopharmaceutics Classification System) and BDDCS (Biopharmaceutics Drug Disposition Classification System) in Drug Development. L.Z. Benet. J. Pharm. Sci. 102, (2013)
34 BDDCS Applied to Over 900 Drugs Leslie Z. Benet, Fabio Broccatelli, and Tudor I. Oprea AAPS Journal 13: (2011)
35 Here we compile the BDDCS classification for 927 drugs, which include 30 active metabolites. Of the 897 parent drugs, 78.8% (707) are administered orally. Where the lowest measured solubility is found this value is reported for 72.7% (513) of these orally administered drugs and a Dose Number is recorded. Measured values are reported for percent excreted unchanged in urine, Log P and Log D7.4 when available. For all 927 compounds, the in silico parameters for predicted Log solubility in water, calculated Log P, Polar Surface Area and the number of hydrogen bond acceptors and hydrogen bond donors for the active moiety are also provided, thereby allowing comparison analyses for both in silico and experimentally measured values. We discuss the potential use of BDDCS to estimate disposition characteristics of novel chemicals (new molecular entities, NMEs) in the early stages of drug discovery and development.
36 Distribution of Drugs on the Market (698 oral IR) vs. Small Molecule NMEs High Solubility Low Solubility NME percentages from a data set of 28,912 medicinal chemistry compounds tested for at least one target and having affinities at µm or less concentrations. High Permeability Low Permeability Class 1 Marketed Drugs 40% NMEs: 18% Class 3 Marketed Drugs 21% NMEs: 22% Class 2 Marketed Drugs 33% NMEs: 54% Class 4 Marketed Drugs 6% NMEs: 6% [L.Z. Benet, J. Pharm. Sci. 102: (2013)] [F. Broccatelli et al., Mol. Pharmaceut. 9: (2012)]
37 Best in silico solubility vs measured VolSurf+ r 2 =0.33 (ALOGPS r 2 = 0.24) Distribution of Drugs on the Market (698 oral IR) vs. Small Molecule NMEs [LZ Benet, F Broccatelli and TI Oprea, AAPS J. 13: (2011)] High Permeability Low Permeability High Solubility Class 1 Marketed Drugs 40% NMEs: 18% 79.3% (55.8%) Class 3 Marketed Drugs 21% NMEs: 22% 90.1% (74.8%) Low Solubility Class 2 Marketed Drugs 33% NMEs: 54% 78.1% (85.1%) Class 4 Marketed Drugs 6% NMEs: 6% 39.5% (82.7%)
38 For either measured or calculated Log P >2, the probability of extensive metabolism is 79.9 and 81.0 %, respectively. For Log P values < 0 the probability of poor metabolism is 84.0 % for M Log P and 83.4 % for CLogP. Distribution of Drugs on the Market (698 oral IR) vs. Small Molecule NMEs [LZ Benet, F Broccatelli and TI Oprea, AAPS J. 13: (2011)] High Permeability Low Permeability High Solubility Class 1 Marketed Drugs 40% NMEs: 18% Class 3 Marketed Drugs 21% NMEs: 22% Low Solubility Class 2 Marketed Drugs 33% NMEs: 54% Class 4 Marketed Drugs 6% NMEs: 6%
39 When Log P values range from 0-2 (31.4% of drugs for M Log P and 27.5% of drugs for CLogP)
40
41 Improving the Prediction of the Brain Disposition of Orally Administered Drugs Using BDDCS F. Broccatelli, C.A. Larregieu, G. Cruciani, T.I. Oprea and L.Z. Benet Advanced Drug Delivery Reviews 64: (2012)
42 From the literature we were able to identify 153 drugs that met three criteria: a) central or lack of central human pharmacodynamic effects were known b) the drug s permeability/metabolism and BDDCS class were identified c) information was available as to whether the drug was or was not a substrate for P-glycoprotein (since it is generally believed that P-gp substrates do not yield central effects)
43 In the analysis we found 18 of the 153 drugs were high permeability BDDCS Class 1 compounds that were also substrates of P-glycoprotein. But of those 18 BDDCS Class 1 drugs, 17 (94.4%) exhibited central pharmacodynamic effects in humans.
44 Class 1 Drugs A major proposition of BDDCS is that Class 1, P450/UGT metabolized drugs are not substrates of clinical relevance for transporters in the intestine, liver, kidney and brain.
45 Another Implication Class 1 compounds will achieve brain concentrations whether this is desired or not for an NME, which could be the rationale for not always wanting Class 1 NMEs.
46 Kola and Landis, 2004
47 But the decrease in attrition due to PK/Bioavailability doesn t mean that we don t have problems to solve, it just means that we have recognized that these problems must be solved. That is, we must optimize the pharmacokinetics and bioavailability of the NME.
48 How can the concepts presented be used in predicting DMPK of an NME? In silico methodology, at present, is not sufficient (except possibly for V ss ). We cannot predict clearance & bioavailability Permeability measures in Caco-2, MDCK or PAMPA vs metoprolol will predict Class 1 & 2 vs. 3 & 4 and thus major route of elimination in humans. Is solubility over the ph range more than 0.2 mg/ml ( i.e., 50 mg highest dose strength) as proposed by Pfizer scientists, defining Class 1 & 3 vs. 2 & 4.
49 Potential DDIs Predicted by BDDCS Class 1: Only metabolic in the intestine and liver Class 2: Metabolic, efflux transporter and efflux transporter-enzyme interplay in the intestine. Metabolic, uptake transporter, efflux transporter and transporter-enzyme interplay in the liver. Class 3 and 4: Uptake transporter, efflux transporter and uptake-efflux transporter interplay
50 Food Effects (High Fat Meals) Fleisher et al., Clin Pharmacokinet.36(3): , 1999 High Permeability High Solubility Class 1 F extent T peak Low Solubility Class 2 F extent T peak Low Permeability Class 3 F extent T peak Class 4 F extent T peak
51 The observed effects of high fat meals on the extent of bioavailability, F extent, is consistent with high fat meals inhibiting transporters in the BDDCS predictions. Even if this is not found to be true, the supposition allows predictions of food effects on drug bioavailability. However, many factors are related to food effects, and the predictions here on F are only 70% of the time.
52 Conclusions Understanding transporter-enzyme interactions in terms of the permeability and solubility of drug compounds offers the potential for predicting: a. Major routes of elimination b. Transporter effects of drug absorption c. Food (High Fat Meal) effects d. Transporter effects on post absorption systemic levels and after i.v. dosing e. Enzyme transporter interplay f. Drug-drug interaction potential and its relationship to enzyme-transporter interplay
53 Conclusions g. Uremic toxins can inhibit hepatic uptake of Class 2 metabolized drugs and Class 3 and 4 biliarily excreted drugs causing decreased clearance. h. The translation of pharmacogenetic differences in metabolic enzymes (genetic polymorphisms) that do not always result in the expected differences in vivo. Phenotype-genotype discordance (as well as changes in the relationship as a function of disease states) may be explained by the effects of transporters on metabolic clearance. i. Obtaining a realistic perspective of new techniques (e.g., predictive ADME, QSAR, microdosing, systems biology). If validation of the technique primarily uses Class 1 drugs, there is no assurance that the technique will work for NMEs.
Biopharmaceutics Drug Disposition Classification System (BDDCS) --- Its Impact and Application
Biopharmaceutics Drug Disposition Classification System (BDDCS) --- Its Impact and Application Leslie Z. Benet, Ph.D. Professor of Bioengineering and Therapeutic Sciences Schools of Pharmacy and Medicine
More informationBiopharmaceutics Drug Disposition Classification System (BDDCS) and Its Application in Drug Discovery and Development
Biopharmaceutics Drug Disposition Classification System (BDDCS) and Its Application in Drug Discovery and Development Leslie Z. Benet, Ph.D. Professor of Bioengineering and Therapeutic Sciences University
More informationLeslie Z. Benet, PhD. Professor of Bioengineering and Therapeutic Sciences Schools of Pharmacy and Medicine University of California San Francisco
Biopharmaceutics Drug Disposition Classification System (BDDCS) and Drug Interactions Leslie Z. Benet, PhD Professor of Bioengineering and Therapeutic Sciences Schools of Pharmacy and Medicine University
More informationDrug disposition classification systems: A comparative review of BDDCS, ECCS and ECCCS
Novartis Drug disposition classification systems: A comparative review of BDDCS, ECCS and ECCCS Birk Poller, Gian Camenisch - Novartis SOLVO - Meet The Experts Transporter Conference April 26, 2018 Drug
More informationBuilding innovative drug discovery alliances. Hepatic uptake and drug disposition o in vitro and in silico approaches
Building innovative drug discovery alliances Hepatic uptake and drug disposition o in vitro and in silico approaches Dr Beth Williamson Evotec AG, 2017 Outline Importance of predicting clearance In vitro
More informationEffects of Uptake and Efflux Transporter Inhibition on Erythromycin Breath Test Results
nature publishing group Effects of Uptake and Efflux Transporter Inhibition on Erythromycin Breath Test Results LA Frassetto 1, S Poon 2, C Tsourounis 2, C Valera 2 and LZ Benet 3 The erythromycin breath
More informationDMPK. APRIL 27 TH 2017 Jan Neelissen Scientific Adviser Science & Technology
DMPK APRIL 27 TH 2017 Jan Neelissen Scientific Adviser Science & Technology What I learned is a good DMPK profile have acceptable water solubility for development be completely absorbed, preferably via
More informationStrategy on Drug Transporter Investigation Why, How, Which & When. Jasminder Sahi
Strategy on Drug Transporter Investigation Why, How, Which & When Jasminder Sahi Intestine Drug Absorption PEPT1 OATPs MCTs AE2 Epithelial Cell MCTs MRP3 Liver Excretion via Liver Kidney MRPs OATPs N PT1
More informationComparison Between the US FDA, Japan PMDA and EMA In Vitro DDI Guidance: Are we Close to Harmonization?
Comparison Between the US FDA, Japan PMDA and EMA In Vitro DDI Guidance: Are we Close to Harmonization? Brian Ogilvie, Ph.D. VP Scientific Consulting XenoTech, LLC bogilvie@xenotechllc.com 14 Jun, 2018
More informationDRUG METABOLISM AND PHARMACOKINETICS (DMPK) Lena Gustavsson, H. Lundbeck A/S, November 2015
DRUG METABOLISM AND PHARMACOKINETICS (DMPK), H. Lundbeck A/S, LEGU@lundbeck.com November 2015 DMPK in Drug Discovery and Development Agenda Introduction Optimizing pharmacokinetic properties Absorption
More informationEvaluation of Drug-Drug Interactions FDA Perspective
Evaluation of Drug-Drug Interactions FDA Perspective Kellie Schoolar Reynolds, Pharm.D. Deputy Director Division of Clinical Pharmacology IV Office of Clinical Pharmacology Office of Translational Sciences
More informationClick to edit Master title style
A Short Course in Pharmacokinetics Chris Town Research Pharmacokinetics Outline Pharmacokinetics - Definition Ideal Pharmacokinetic Parameters of a New Drug How do we optimize PK for new compounds Why
More informationThe ADME properties of most drugs strongly depends on the ability of the drug to pass through membranes via simple diffusion.
1 MEDCHEM 562 Kent Kunze Lecture 1 Physicochemical Properties and Drug Disposition The ADME properties of most drugs strongly depends on the ability of the drug to pass through membranes via simple diffusion.
More informationCaveat: Validation and Limitations of Phenotyping Methods for Drug Metabolizing Enzymes and Transporters
Caveat: Validation and Limitations of Phenotyping Methods for Drug Metabolizing Enzymes and Transporters Uwe Fuhr, University Hospital Cologne 1 How to Safeguard that Metrics Reflect E/T Activity? in healthy
More informationT Eley, Y-H Han, S-P Huang, B He, W Li, W Bedford, M Stonier, D Gardiner, K Sims, P Balimane, D Rodrigues, RJ Bertz
IN VIVO AND IN VITRO ASSESSMENT OF ASUNAPREVIR (ASV; BMS-650032) AS AN INHIBITOR AND SUBSTRATE OF ORGANIC ANION TRANSPORT POLYPEPTIDE (OATP) TRANSPORTERS IN HEALTHY VOLUNTEERS T Eley, Y-H Han, S-P Huang,
More informationEffect of Multiple-Dose Ketoconazole and the Effect of Multiple-Dose Rifampin on Pharmacokinetics (PK) of the HCV NS3 Protease Inhibitor Asunaprevir
Effect of Multiple-Dose Ketoconazole and the Effect of Multiple-Dose Rifampin on Pharmacokinetics (PK) of the HCV NS3 Protease Inhibitor Asunaprevir Eley T, 1 He B, 1 Huang S-P, 2 Stonier M, 1 Bedford
More informationIntroduction to Pharmacokinetics (PK) Anson K. Abraham, Ph.D. Associate Principal Scientist, PPDM- QP2 Merck & Co. Inc., West Point, PA 5- June- 2017
Introduction to Pharmacokinetics (PK) Anson K. Abraham, Ph.D. Associate Principal Scientist, PPDM- QP2 Merck & Co. Inc., West Point, PA 5- June- 2017 1 Outline Definition & Relevance of Pharmacokinetics
More informationThe Influence of Physicochemical Properties on ADME
The Influence of Physicochemical Properties on ADME Iain Martin Iain Martin; Physchem Forum 2 1 Physchem and ADME A quick tour of the influence of physicochemical properties on: Absorption Distribution
More informationUsing Accelerator Mass Spectrometry to Explain the Pharmacokinetics of Vismodegib Cornelis E.C.A. Hop
Using Accelerator Mass Spectrometry to Explain the Pharmacokinetics of Vismodegib Cornelis E.C.A. Hop Topics to be Addressed Why AMS? AMS for mass balance studies with vismodegib AMS for absolute bioavailability
More informationCytochrome P450 Drug Interaction Table Flockhart Table
Cytochrome P450 Drug Interaction Table Flockhart Table The table contains lists of drugs in columns under the designation of specific cytochrome P450 isoforms. CYTOCHROME P450 DRUG INTERACTION TABLE A
More informationChristian Wagner (Autor) Predicting the Oral Absorption of Poorly Soluble Drugs
Christian Wagner (Autor) Predicting the Oral Absorption of Poorly Soluble Drugs https://cuvillier.de/de/shop/publications/6557 Copyright: Cuvillier Verlag, Inhaberin Annette Jentzsch-Cuvillier, Nonnenstieg
More informationApplied Biopharmaceutics & Pharmacokinetics Sixth Edition
Applied Biopharmaceutics & Pharmacokinetics Sixth Edition Hill Leon Shargel, PHD, RPh Applied Biopharmaceutics, LLC Raleigh, North Carolina Affiliate Associate Professor, School of Pharmacy Virginia Commonwealth
More informationCurrent Approaches and Applications of Phenotyping Methods for Drug Metabolizing Enzymes and Transporters
Current Approaches and Applications of Phenotyping Methods for Drug Metabolizing Enzymes and Transporters Uwe Fuhr, University Hospital Cologne 1 Definition Phenotyping is quantifying the in vivo activity
More informationBasic Biopharmaceutics, Pharmacokinetics, and Pharmacodynamics
Basic Biopharmaceutics, Pharmacokinetics, and Pharmacodynamics Learning Outcomes Define biopharmaceutics Describe 4 processes of pharmacokinetics Describe factors that affect medication absorption Describe
More informationDefine the terms biopharmaceutics and bioavailability.
Pharmaceutics Reading Notes Define the terms biopharmaceutics and bioavailability. Biopharmaceutics: the area of study concerning the relationship between the physical, chemical, and biological sciences
More informationPhysiologically-Based Simulation of Daclatasvir Pharmacokinetics With Antiretroviral Inducers and Inhibitors of Cytochrome P450 and Drug Transporters
Physiologically-Based Simulation of Daclatasvir Pharmacokinetics With Antiretroviral Inducers and Inhibitors of Cytochrome P450 and Drug Transporters Qi Wang, Wenying Li, Ming Zheng, Timothy Eley, Frank
More informationVolume 1(3) May-June 2013 Page 351
ISSN: 2321-5674(Print) BIOAVAILABILITY: CRITERIA FOR APPROVING A DRUG PRODUCT FOR MARKETING Sandhya Singh 1, Faheem Ajmal Ansari 1, Shravan Paswan 2*, Rnjan Kumar Sharma 2, Alok Ranjan Gaur 3 1 Azad Institute
More information1 Introduction: The Why and How of Drug Bioavailability Research
j1 1 Introduction: The Why and How of Drug Bioavailability Research Han van de Waterbeemd and Bernard Testa Abbreviations ADME EMEA FDA NCE PD P-gp PK R&D Absorption, distribution, metabolism, and excretion
More informationWHY... 8/21/2013 LEARNING OUTCOMES PHARMACOKINETICS I. A Absorption. D Distribution DEFINITION ADME AND THERAPEUIC ACTION
PHARMACOKINETICS I Absorption & Distribution LEARNING OUTCOMES By the end of the lecture students will be able to.. Dr Ruwan Parakramawansha MBBS, MD, MRCP(UK),MRCPE, DMT(UK) (2013/08/21) Define pharmacokinetics,
More informationDrug Absorption and Bioavailability
Drug Absorption and Bioavailability Juan J.L. Lertora, M.D., Ph.D. Director Clinical Pharmacology Program October 4, 2012 Office of Clinical Research Training and Medical Education National Institutes
More informationDistinguishing between the Permeability Relationships with Absorption and Metabolism To Improve BCS and BDDCS Predictions in Early Drug Discovery
This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. pubs.acs.org/molecularpharmaceutics
More informationDevelopment of Canagliflozin: Mechanistic Absorption Modeling During Late-Stage Formulation and Process Optimization
Development of Canagliflozin: Mechanistic Absorption Modeling During Late-Stage Formulation and Process Optimization Nico Holmstock Scientist, Janssen R&D M CERSI 2017, BALTIMORE (USA) Canagliflozin An
More informationPharmacokinetic Modeling & Simulation in Discovery and non-clinical Development
Pharmacokinetic Modeling & Simulation in Discovery and non-clinical Development Where do we stand? Disclaimer I am not a bioinformatician, mathematician or biomedical engineer. I am a simple minded pharmacist,
More informationBasic Concepts of TDM
TDM Lecture 1 5 th stage What is TDM? Basic Concepts of TDM Therapeutic drug monitoring (TDM) is a branch of clinical pharmacology that specializes in the measurement of medication concentrations in blood.
More informationPharmacokinetics in Drug Development. Edward P. Acosta, PharmD Professor & Director Division of Clinical Pharmacology Director, CCC PK/PD Core
Pharmacokinetics in Drug Development Edward P. Acosta, PharmD Professor & Director Division of Clinical Pharmacology Director, CCC PK/PD Core Finding new drugs: A crap shoot Clinical Development Phase
More informationStrategies for Developing and Validating PBPK Models for Extrapolation to Unstudied Population
Strategies for Developing and Validating PBPK Models for Extrapolation to Unstudied Population Nina Isoherranen Department of Pharmaceutics University of Washington Processes driving drug disposition are
More informationFDA s Clinical Drug Interaction Studies Guidance (2017 Draft Guidance)
FDA s Clinical Drug Interaction Studies Guidance (2017 Draft Guidance) Kellie S. Reynolds, Pharm.D. Deputy Director, Division of Clinical Pharmacology IV Office of Clinical Pharmacology (OCP) Office of
More informationTransporters DDI-2018
Transporters DDI-2018 Mark S. Warren, Ph.D. June 16, 2018 Senior Director of Assay Services DDI-2018: 21 st Conference on DDIs FDA guidance documents: A 21 year history 1997 2006 2012 2017 Each year, large
More informationHTPK: Conducting PK modeling and
HTPK: Conducting PK modeling and simulations at high speed November 5, 2018 Robert Fraczkiewicz, David Miller, Marvin Waldman, Robert D. Clark Slide 1 Session Description and Objectives HTPK lightens the
More informationBasic Pharmacokinetics and Pharmacodynamics: An Integrated Textbook with Computer Simulations
Basic Pharmacokinetics and Pharmacodynamics: An Integrated Textbook with Computer Simulations Rosenbaum, Sara E. ISBN-13: 9780470569061 Table of Contents 1 Introduction to Pharmacokinetics and Pharmacodynamics.
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 informationPharmacokinetics and bioavailability derived from various body fluids. Saliva samples instead of plasma samples
Pharmacokinetics and bioavailability derived from various body fluids Saliva samples instead of plasma samples Willi Cawello, Schwarz BioSciences, Monheim am Rhein 1 Overview Introduction Sampling tissues/fluids
More informationSection 5.2: Pharmacokinetic properties
Section 5.2: Pharmacokinetic properties SmPC training presentation Note: for full information refer to the European Commission s Guideline on summary of product characteristics (SmPC) SmPC Advisory Group
More informationRISK FACTORS AND DRUG TO STATIN-INDUCED MYOPATHY
RISK FACTORS AND DRUG INTERACTION PREDISPOSING TO STATIN-INDUCED MYOPATHY Assist. Prof. Dr. Verawan Uchaipichat Clinical Pharmacy Department Khon Kaen University Advanced Pharmacotherapy 2012 Updated d
More informationBASIC PHARMACOKINETICS
BASIC PHARMACOKINETICS MOHSEN A. HEDAYA CRC Press Taylor & Francis Croup Boca Raton London New York CRC Press is an imprint of the Taylor & Francis Group, an informa business Table of Contents Chapter
More informationIPAC-RS/UF Orlando Inhalation Conference March 20, S.T. Horhota 1, C.B. Verkleij 2, P.J.G. Cornelissen 2, L. Bour 3, A. Sharma 3, M.
IPAC-RS/UF Orlando Inhalation Conference March 20, 2014 Case Study: Pharmacokinetics and Pharmacodynamics of Tiotropium and Salmeterol Following Parallel Administration in COPD Patients Using Different
More informationPHARMACOLOGY-1 PHL-313. Ali Alhoshani Office: 2B 84
PHARMACOLOGY-1 PHL-313 Ali Alhoshani ahoshani@ksu.edu.sa http://fac.ksu.edu.sa/ahoshani Office: 2B 84 General rules Reference: General rules Email [PHL313-1 st Semester 38-39] Student ID- Question Example
More informationMODELING MECHANISM BASED INACTIVATION USING PBPK JAN WAHLSTROM DIRECTOR, PRECLINICAL
MODELING MECHANISM BASED INACTIVATION USING PBPK JAN WAHLSTROM DIRECTOR, PRECLINICAL ABSTRACT Quantitative prediction of the magnitude of drug-drug interactions (DDI) is critical to underwriting patient
More informationControlling ADME through Chemical Design. Marty Mulvihill Chris Vulpe
Controlling ADME through Chemical Design Marty Mulvihill Chris Vulpe ADME Chemical Processes in ADME Wang and Skolnik, Chemistry and Biodiversity, 2009, 1887. Controlling toxicity through ADME Toward molecular
More informationDetermination of bioavailability
Pharmaceutics 2 Bioavailability Bioavailability is the rate and extent to which an administered drug reaches the systemic circulation. For example, if 100 mg of a drug is administered orally and 70 mg
More informationDRUG-DRUG INTERACTIONS OF GLECAPREVIR AND PIBRENTASVIR WITH PRAVASTATIN, ROSUVASTATIN, OR DABIGATRAN ETEXILATE
DRUG-DRUG INTERACTIONS OF GLECAPREVIR AND PIBRENTASVIR WITH PRAVASTATIN, ROSUVASTATIN, OR DABIGATRAN ETEXILATE Matthew P. Kosloski, Weihan Zhao, Hong Li, Stanley Subhead Wang, Calibri Joaquin 14pt, Valdes,
More informationWelcome to the webinar... We will begin shortly
Welcome to the webinar... We will begin shortly Evaluation of Ketoconazole and Its Alternative Clinical CYP3A4/5 Inhibitors as Inhibitors of Drug Transporters: The In Vitro Effects of Ketoconazole, Ritonavir,
More informationPrinciples of Toxicokinetics/Toxicodynanics
Biochemical and Molecular Toxicology ENVR 442; TOXC 442; BIOC 442 Principles of Toxicokinetics/Toxicodynanics Kim L.R. Brouwer, PharmD, PhD kbrouwer@unc.edu; 919-962-7030 Pharmacokinetics/ Toxicokinetics:
More informationTracer studies in GSK for Discovery and Development
Tracer studies in GSK for Discovery and Development 3 rd June 2010...a ripple or a wavefront? Graeme Young, DMPK, GlaxoSmithKline R&D, Ware, UK Outline Historical use of AMS at GSK variety of ADME studies;
More informationDrug Absorption and Bioavailability
Drug Absorption and Bioavailability Juan J.L. Lertora, M.D., Ph.D. Director Clinical Pharmacology Program October 1, 2015 Office of Clinical Research Training and Medical Education National Institutes
More informationDrug Absorption and Bioavailability
Drug Absorption and Bioavailability Juan J.L. Lertora, M.D., Ph.D. Director Clinical Pharmacology Program October 1, 2015 Office of Clinical Research Training and Medical Education National Institutes
More informationBIOEQUIVALENCE AND THERAPEUTIC EQUIVALENCE. Soula Kyriacos, B.Pharm, PhD Head R&D, Pharmaline November 2016
BIOEQUIVALENCE AND THERAPEUTIC EQUIVALENCE Soula Kyriacos, B.Pharm, PhD Head R&D, Pharmaline November 2016 Introduction Early 1970 s FDA regulations for submission of BA data 1984 US Congress passed the
More informationPharmacokinetics for Physicians. Assoc Prof. Noel E. Cranswick Clinical Pharmacologist Royal Children s Hospital Melbourne
Pharmacokinetics for Physicians Assoc Prof. Noel E. Cranswick Clinical Pharmacologist Royal Children s Hospital Melbourne The Important Therapeutic Questions What drug? What dose? How long? Drug Dosage
More informationUSING PBPK MODELING TO SIMULATE THE DISPOSITION OF CANAGLIFLOZIN
USING PBPK MODELING TO SIMULATE THE DISPOSITION OF CANAGLIFLOZIN Christophe Tistaert PDMS Pharmaceutical Sciences Preformulation & Biopharmaceutics AAPS 2015, FLORIDA (USA) Canagliflozin An orally active
More informationPharmacokinetic and absolute bioavailability studies in early clinical development using microdose and microtracer approaches.
Pharmacokinetic and absolute bioavailability studies in early clinical development using microdose and microtracer approaches. Lloyd Stevens PhD Senior Research Fellow Pharmaceutical Profiles Nottingham,
More informationCytochrome P450 Suppression in Human Hepatocyte Cultures by Small and Large Molecules. George Zhang, Ph.D. April 18, 2012
Cytochrome P450 Suppression in Human Hepatocyte Cultures by Small and Large Molecules George Zhang, Ph.D. April 18, 2012 Presentation Overview Regulatory guidance Brief review on drug-drug (Disease) interactions
More informationCurrent and Emerging Transporter Regulatory Themes in Drug Development: Relevance to Understanding PK/PD, DDIs, and Toxicity
Current and Emerging Transporter Regulatory Themes in Drug Development: Relevance to Understanding PK/PD, DDIs, and Toxicity Maciej Zamek-Gliszczynski, Ph.D. 1940 s Probenecid & anion secretion 1950 s
More informationBristol-Myers Squibb HCV DAAs: Review of Interactions Involving Transporters. Timothy Eley. 21 May 2014
Bristol-Myers Squibb HCV DAAs: Review of Interactions Involving Transporters Timothy Eley 15th HIV/HEPPK Workshop 21 May 2014 Disclosures T Eley is a full time employee and stockholder of Bristol-Myers
More informationPursuing the holy grail of predicting and verifying tissue drug concentrations: A proteomics and PET imaging approach
Pursuing the holy grail of predicting and verifying tissue drug concentrations: A proteomics and PET imaging approach Jashvant (Jash) Unadkat Milo Gibaldi Endowed Professor Dept. of Pharmaceutics School
More informationPractical Application of PBPK in Neonates and Infants, Including Case Studies
Practical Application of PBPK in Neonates and Infants, Including Case Studies Presented at the conference : Innovative Approaches to Pediatric Drug Development and Pediatric Medical Countermeasures: A
More informationUNIVERSITY OF THE WEST INDIES, ST AUGUSTINE
UNIVERSITY OF THE WEST INDIES, ST AUGUSTINE FACULTY OF MEDICAL SCIENCES SCHOOL OF PHARMACY BACHELOR OF SCIENCE IN PHARMACY DEGREE COURSE SYLLABUS COURSE TITLE: COURSE CODE: BIOPHARMACEUTICS, NEW DRUG DELIVERY
More informationMycophénolate mofétil
Mycophénolate mofétil O OH CH 3 O O-desmethyl O glucosides OH CH 3 OCH 3 CH 3 CYP 3A UGT2B7 C O HO O HO AcMPAG (acyl-glucuronide) ACTIF TOXIQUE O O CH 3 OCH 3 Mycophenolate (MPA) OH COOH UGT enzymes COOH
More informationPharmacogenetics and Pharmacokinetics
Chapter 2 Pharmacogenetics and Pharmacokinetics Mauro Saivezzo/ShutterStock, Inc. L earning O bjectives Upon completion of this chapter, the student will be able to: 1. Recognize the influence of genetic
More informationA novel microdose approach to assess bioavailability, intestinal absorption, gut metabolism, and hepatic clearance of simeprevir in healthy volunteers
A novel microdose approach to assess bioavailability, intestinal absorption, gut metabolism, and hepatic clearance of simeprevir in healthy volunteers Sivi Ouwerkerk-Mahadevan, 1 Jan Snoeys, 1 Alex Simion,
More informationSaliva Versus Plasma Bioequivalence of Rusovastatin in Humans: Validation of Class III Drugs of the Salivary Excretion Classification System
Drugs R D (2015) 15:79 83 DOI 10.1007/s40268-015-0080-1 ORIGINAL RESEARCH ARTICLE Saliva Versus Plasma Bioequivalence of Rusovastatin in Humans: Validation of Class III Drugs of the Salivary Excretion
More informationExcipient Interactions Relevant For BCS Biowaivers Peter Langguth
Excipient Interactions Relevant For BCS Biowaivers Peter Langguth Department of Pharmaceutical Technology and Biopharmaceutics, Johannes Gutenberg University Mainz, Germany 3rd Symposium on Harmonization
More informationViera Lukacova Director, Simulation Sciences
Use of In Silico Mechanistic Models to Support Interspecies Extrapolation of Oral Bioavailability and Formulation Optimization: Model Example Using GastroPlus Viera Lukacova Director, Simulation Sciences
More informationUse of PBPK in simulating drug concentrations in pediatric populations: Case studies of Midazolam and Gabapentin
Use of PBPK in simulating drug concentrations in pediatric populations: Case studies of Midazolam and Gabapentin WORKSHOP ON MODELLING IN PAEDIATRIC MEDICINES April 2008 Viera Lukacova, Ph.D. Walter Woltosz,
More informationBCS: Dissolution Testing as a Surrogate for BE Studies
BCS: Dissolution Testing as a Surrogate for BE Studies Dirk M Barends National Institute of Public Health and the Environment The Netherlands APV / IKEV Seminar on Bioavailability and Bioequivalence, Istanbul,
More informationBIOPHARMACEUTICS and CLINICAL PHARMACY
11 years papers covered BIOPHARMACEUTICS and CLINICAL PHARMACY IV B.Pharm II Semester, Andhra University Topics: Absorption Distribution Protein binding Metabolism Excretion Bioavailability Drug Interactions
More informationClinical Pharmacology of DAA s for HCV: What s New and What s in the Pipeline
Clinical Pharmacology of DAA s for HCV: What s New and What s in the Pipeline Anita Mathias, PhD Clinical Pharmacology, Gilead Sciences 14 th Int. Workshop on Clinical Pharmacology of HIV Therapy April
More informationUsing virtual populations to solve drug development problems. Iain Gardner Head of Translational DMPK Science SIMCYP
Using virtual populations to solve drug development problems Iain Gardner Head of Translational DMPK Science SIMCYP Prediction of human PK (PD) in virtual individuals In vitro system In vitro CLu int Scaling
More informationTake-Home Exam Distributed: October 19, 2012, at 2:30 p.m. Due: October 24, 2012, at 1:30 p.m.
20.201 Take-Home Exam Distributed: October 19, 2012, at 2:30 p.m. Due: October 24, 2012, at 1:30 p.m. Directions: This take-home exam is to be completed without help from any other individual except Drs.
More informationComplexities of Hepatic Drug Transport: How Do We Sort It All Out?
Complexities of Hepatic Drug Transport: How Do We Sort It All Out? Keith A. Hoffmaster Pfizer Research Technology Center Cambridge, MA NEDMDG 2005 Summer Symposium 06.08.2005 The Challenge Intestinal uptake
More informationApplication and Experience in the EU of the BCS Concept in the review of new generics & variations
Application and Experience in the EU of the BCS Concept in the review of new generics & variations Dirk M Barends National Institute of Public Health and the Environment The Netherlands APV / IKEV Seminar
More informationSuitability of Digoxin as a P Glycoprotein Probe: Implications of Other Transporters on Sensitivity and Specificity
Review Suitability of Digoxin as a P Glycoprotein Probe: Implications of Other Transporters on Sensitivity and Specificity The Journal of Clinical Pharmacology XX(XX) 1 11 2013, The American College of
More informationPK-UK Challenges and benefits of using PBPK to evaluate an IVIVC for drugs with nonideal solubility and/or permeability. Bath, November 2014
PK-UK 2014 Challenges and benefits of using PBPK to evaluate an IVIVC for drugs with nonideal solubility and/or permeability Bath, November 2014 Prof. Dr. Jennifer Dressman Dressman Bath 2014 Why IVIVC
More informationUnderstand the physiological determinants of extent and rate of absorption
Absorption and Half-Life Nick Holford Dept Pharmacology & Clinical Pharmacology University of Auckland, New Zealand Objectives Understand the physiological determinants of extent and rate of absorption
More informationDrug Interactions, from bench to bedside
Drug Interactions, from bench to bedside Candidate to Market, The Paterson Institute for Cancer Research, Manchester, UK Michael Griffin PhD Overview of presentation To understand the importance of drug-drug
More informationAssessing the role of hepatic uptake in drug clearance - Pharmacokinetic and experimental considerations
Assessing the role of hepatic uptake in drug clearance - Pharmacokinetic and experimental considerations Peter Webborn ISSX Short course Toronto 2013 1 Defining the why, when and how of Transporter studies
More informationWe will begin momentarily at 2pm ET. Slides available now! Recordings will be available to ACS members after one week.
We will begin momentarily at 2pm ET Slides available now! Recordings will be available to ACS members after one week. www.acs.org/acswebinars Contact ACS Webinars at acswebinars@acs.org 1 Have Questions?
More informationThe Future of In Vitro Systems for the Assessment of Induction and Suppression of Enzymes and Transporters
The Future of In Vitro Systems for the Assessment of Induction and Suppression of Enzymes and Transporters AAPS, San Diego November 6 th, 2014 Andrew Parkinson, XPD Consulting Lisa Almond, Simcyp-Certara
More informationcationic molecule, paracellular diffusion would be thought of as its primary mode of transport across epithelial cells.
ABSTRACT Metformin is the most widely prescribed anti-hyperglycemic agent for Type 2 Diabetes Mellitus (T2DM). Despite its frequent use, the intestinal absorption mechanism of this orally administered
More informationClinical Pharmacology of DAA s for HCV: What s New & What s In Pipeline
Clinical Pharmacology of DAA s for HCV: What s New & What s In Pipeline Kirk Bertelsen, PhD Clinical Pharmacology Janssen Pharmaceuticals, Research & Development 4/24/2013 1 Incivo Simeprevir 2 Janssen
More informationAltered GI absorption in special populations: An industry perspective
Altered GI absorption in special populations: An industry perspective Cordula Stillhart and Neil J. Parrott F. Hoffmann La Roche Ltd, Basel (CH) UNGAP WG meeting, Leuven (B) 8 March 2018 Current challenges
More informationOsnove farmakokinetike. Aleš Mrhar. Prirejeno po. A First Course in Pharmacokinetics and Biopharmaceutics by David Bourne,
Osnove farmakokinetike Aleš Mrhar Prirejeno po A First Course in Pharmacokinetics and Biopharmaceutics by David Bourne, College of Pharmacy, University of Oklahoma Pharmacokinetics/Pharmacodynamics Pharmacodynamics
More informationThe BCS: Where Do We Go from Here?
The BCS: Where Do We Go from Here? Jennifer Dressman,* James Butler, John Hempenstall, and Christos Reppas Since the Biopharmaceutics Classification System (BCS) was introduced several years ago, it has
More informationSimulation of Membrane and Cell Culture Permeability and Transport. Michael B. Bolger and Viera Lukacova Simulations Plus, Inc.
Simulation of Membrane and Cell Culture Permeability and Transport Michael B. Bolger and Viera Lukacova Simulations Plus, Inc. utline Models of microscopic membrane kinetics Calculation of membrane entry
More informationEVALUATION OF DRUG-DRUG INTERACTION POTENTIAL BETWEEN SACUBITRIL/VALSARTAN (LCZ696) AND STATINS USING A PHYSIOLOGICALLY- BASED PHARMACOKINETIC MODEL
Drug metabolism and Pharmacokinetics/PK Sciences EVALUATIN F DRUG-DRUG INTERACTIN PTENTIAL BETWEEN SACUBITRIL/VALSARTAN (LCZ696) AND STATINS USING A PHYSILGICALLY- BASED PHARMACKINETIC MDEL Imad Hanna,
More informationErik Mogalian, Polina German, Chris Yang, Lisa Moorehead, Diana Brainard, John McNally, Jennifer Cuvin, Anita Mathias
Evaluation of Transporter and Cytochrome P450-Mediated Drug-Drug Interactions Between Pan-Genotypic HCV NS5A Inhibitor GS-5816 and Phenotypic Probe Drugs Erik Mogalian, Polina German, Chris Yang, Lisa
More informationAbsolute bioavailability and pharmacokinetic studies in early clinical development using microdose and microtracer approaches.
Absolute bioavailability and pharmacokinetic studies in early clinical development using microdose and microtracer approaches. Dr Lloyd Stevens Senior Research Fellow Pharmaceutical Profiles Nottingham,
More informationDrug Penetration to Sanctuary Sites Oral vs. IV Administration
Drug Penetration to Sanctuary Sites Oral vs. IV Administration Courtney V. Fletcher, Pharm.D. Dean, College of Pharmacy Professor, Department of Pharmacy Practice and Division of Infectious Diseases University
More informationStimulate your kinetic understanding Permeability Binding Metabolism Transporters
Stimulate your kinetic understanding Permeability Binding Metabolism Transporters www.simulations-plus.com +1-661-723-7723 What is MembranePlus? MembranePlus is an advanced, yet easy-to-use, modeling and
More informationMetformin IR tablets: partial in vitro dissolution profiles differences do not preclude in vivo bioequivalence
Metformin IR tablets: partial in vitro dissolution profiles differences do not preclude in vivo bioequivalence Eva Troja Quality Control Department Profarma SH.A. Pharmaceutical Industry Tirana, Albania
More informationBiopharmaceutics. Tips Worth Tweeting. Contributor: Sandra Earle
Biopharmaceutics C H A P T E R 2 Contributor: Sandra Earle The physiochemical properties of drugs determine how they will move and interact with the body. By understanding a few principles, predictions
More information