poor solubility and poor permeability unknown whether poor BA is due to poor solubility or antiglaucoma medicine for biowaiver Not eligible

Transcription

1 Table 1 Substances on the WHO Model List of Essential Medicines (EML) Medicine a abacavir 200 mg high low antiretroviral acetazolamide 250 mg low low (?) 4/2 antiglaucoma acetylsalicylic acid 500 mg high high NSAID, antimigraine acetylsalicylic acid 100 mg high high antithrombotic aciclovir 200 mg high low antiherpes s albendazole 400 mg low low (?) 4/2 anthelminthic allopurinol 100 mg high high gout aluminium hydroxide 500 mg NR NA antacid NSAID, Non-steroidal anti-infl ammatory drug; BA, bioavailability. chewable tablet; used for local effect 402

2 amiloride hydrochloride 5 mg high high diuretic amitriptyline hydrochloride 25 mg (1) high high amlodipine 5 mg high high antihypertensive amodiaquine (base) 200 mg high borderline BA > 75% 3/ CYP2C8 polymorphism, increased risk for agranulocytosis liver toxicity antimalarial amoxicillin (a) + clavulanic acid (c) (a) 500 mg + (c) 125 mg (a) high + (c) high (a) high + (c) borderline absorption >73% (radioactive excretion) (a) 1 + (c) 3/ antibacterial amoxicillin anhydrous 500 mg high high antibacterial artemether (a) + lumefantrine (l) (a) 20 mg + (l) 120 mg (a l) unknown low (a l) (a) 4/3 + (l) 4/3 antimalarial ascorbic acid 50 mg high high vitamin atenolol 100 mg high low antianginal, antihypertensive, antiarrhythmic used in heart failure BA, bioavailability. extent of fi rstpass metabolism uncertain combination should be tested clavulanic acid requirements 403

3 Medicine a azithromycin 500 mg low low (?) 4/2 antibacterial benznidazole 100 mg high low American trypanosomiasis biperiden hydrochloride 2 mg high insuffi cient literature 3/ antiparkinson carbamazepine 200 mg low (neutral) high 2 antiepileptic, scored tablet cefi xime 400 mg low low (?) 4/2 antibacterial chloramphenicol 250 mg high low narrow therapeutic index antibacterial chloroquine phosphate or sulfate 150 mg high high DMARD, antimalarial BA, bioavailability; DMRD, disease modifying antirheumatic drug. 404

4 chlorphenamine hydrogen maleate 4 mg high BA 25-59%, fi rst pass 3/ CYP2D6 polymorphism antiallergic extent of fi rstpass metabolism uncertain chlorpromazine hydrochloride 100 mg high low ciprofl oxacin hydrochloride 250 mg high BA 70 82%, possible fi rst pass, high in Caco-2 cells 3/ antibacterial extent of fi rstpass metabolism uncertain clofazimine 100 mg insuffi cient literature low 4/3 at present antileprosy clomifene citrate 50 mg high insuffi cient literature 3/ ovulation inducer clomipramine hydrochloride 25 mg high 66% excreted in the urine, the remainder being eliminated in the faeces 3/ lack of absolute bioavailability data cloxacillin (as sodium salt) 1000 mg high low antibacterial codeine phosphate 30 mg high low risk of abuse opioid analgesic, diarrhoea in adults dapsone 100 mg low (weak base) high 2 G6PD defi - ciency antileprosy diazepam 5 mg high high scored tablet BA, Bioavailability; G6PD, glucose-6-phosphate dehydrogenase. 405

5 Medicine a didanosine 200 mg high low antiretroviral didanosine 400 mg high low 3 see comment antiretroviral digoxin 250 μg high high antiarrhythmic used in heart failure diloxanide furoate 500 mg low (2) low (?) 4/2 antiprotozoal doxycycline hydrochloride 100 mg high high antibacterial efavirenz 200 mg low (1) low (?) 4/2 antiretroviral enalapril 2.5 mg high low antihypertensive BA, Bioavailability. buffered chewable, dispersible tablet unbuffered enteric coated capsule not eligible for biowaiver in this dosage form i 406

6 ergocalciferol 1.25 mg ( IU) high low vitamin erythromycin stearate + ethylsuccinate 250 mg low low 4 antibacterial ethambutol hydrochloride 400 mg high low risk of dose-related ototoxicity antituberculosis ethinylestradiol 50 μg high borderline, BA 40 50%, fi rst pass 3/ estrogen ethinylestradiol (e) + levonorgestrel (l) 30 μg μg high (e) borderline, BA 40 50%, fi rst pass + (l) high 3/ hormonal contraceptive ethinylestradiol (e) + norethisterone (n) 35 μg + 1 mg high (e) borderline, BA 40 50%, fi rst pass + (n) high 3/ hormonal contraceptive ferrous salt equivalalent to 60 mg iron high (see footnote) low antianaemia BA, Bioavailability; GI, gastrointestinal. extent of fi rstpass metabolism uncertain extent of fi rst-pass metabolism uncertain; combination should be tested according to ethinylestradiol requirements extent of fi rst-pass metabolism uncertain; combination should be tested ethinylestradiol requirements commonly used salts: see footnote 407

7 Medicine a ferrous salt (fs) + folic acid (fa) equivalent to 60 mg iron μg folic acid (fs) high + (fa) high (fs) low + (fa) low (urinary recovery 28.5%) (2) 3 + 3/ antianaemia (during pregnancy) fl uconazole 50 mg high high antifungal folic acid 5 mg high low (?) 3/ antianaemia furosemide 40 mg low low (?) 4/2 highly variable BA used in heart failure, diuretic glibenclamide 5 mg low low (?) 4/2 antidiabetic agent NSAID, Non-steroidal anti-infl ammatory drugs; GI, gastrointestinal. lack of absolute bioavailability data; commonly used salts: see footnote; combination should be tested ferrous salt requirements lack of absolute bioavailability data 408

8 glyceryl trinitrate 500 μg high sublingual application, permeability in the oral cavity more important than GI local permeability 3/1 NA h absorption antianginal sublingual application griseofulvin 250 mg low (neutral) high 2 antifungal haloperidol 2 mg borderline < 0.01 mg/ml 2 low 4/3 hydralazine hydrochloride 50 mg high low antihypertensive hydrochlorothiazide 25 mg high low antihypertensive, diuretic used in heart failure scored tablet ibuprofen 400 mg low, weak acid (pk a 4.4, 5.2) high NSAID, antimigraine indinavir sulfate 400 mg low low (?) 4/2 CYP 450 3A4, food effect ( ) antiretroviral D:S, Dose:solubility ratio; BA, bioavailability. 409

9 Medicine a iopanoic acid 500 mg low, weak acid (pk a 4.8) (2) high 2 radiocontrast media Insuffi ciently soluble in water (15 μg/ml) to be eligible for biowaiver isoniazid 300 mg high borderline 3/ antituberculosis isoniazid (i) + ethambutol (e) (i) 150 mg + (e) 400 mg (i) high + (e) high (i) borderline + (e) low (i) 3/1 + (e) 3 See footnote g ocular toxicity antituberculosis isosorbide dinitrate 5 mg high sublingual application, permeability in the oral cavity more important than GI antianginal permeability 3/1 NAh sublingual ivermectin 6 mg practically insoluble in water 3 D:S > 6000 ml low (?) 4/2 antifi larial scored tablet; lamivudine 150 mg high high antiretroviral BA, bioavailability; GI, gastrointestinal; D:S, Dose: solubility ratio. 410