ARS 190 QREMAKSUES RAL A RR aa: ee 3 nen] ox 1. Answer each of the following questions based on the basic model for drug absorption, metabolism, and disposition as shown below. (14 4) Excreted Drug a Excretion Drgat | Absoroon [pein | absorption |_____y] De site yo Metabolism Metabolites () What does it indicate if 100% of unGharifed dria is FeeqyetU inte urine following oral administration? (b) When does drug in the body reach a pealGoncentation ‘following administration of an oral dose? (c) When does the rate of change of drug if the(body by speck the Yate of absorption? (8) When sth mt of change of rn be “pes Si esa fe cna? 2. the disposition of drug ater iv dk dn 4194 si ose in « newborn infant fllows one compartment pharmacokinetics, where nade drug cdylodntiation can be described by Cp = 140 2% Cp (ng/mL) is the plasma concentration of dnig, af! PORTE) fepregents ‘the time. (12 47) (a) Estimate the half-life of the drug. = (b) Caelate the volume of distin, (©)Eaimate the ol eeaance (@) Estimate the total area under the plasma concenttation-time curve, 3. The following figure shows the plasma drug concentration in the body with time following oral ingestion of a single dose of drug. Draw a figure identical to that for each question, and then draw another curve that shows ‘the effect of each of the following alternations in pharmacokinetic parameters. In addition, you need to describe in detail how these changes affect the other pharmacokinetic parameters, too. (12 4) ‘acme. Drag Condition (@ Fimereased, k decreased (by ka increased (©) CL increased, k increased BGFAH + 190 BHUESASUSFRALEBES ROR Be: Same ast 190 HZ R22 FR 4. In evaluating different dosage forms of procainamide obtained the following AUC and cumulative urine ‘excretion data listed in following table. (12 2) Route Dose ‘AUC ‘Amount Exereted (0-48 hr) (oy (mg VL) (my i. 500 Ba 332. oral formulation 1 1000 209 586 formulation 2 1000 199 554 (a) Estimate both the absolute and relative availabilities of formulation 2 from both plasma and urine data ‘What are the assumptions made in your calculations? (©) The haf ite of procainamide found inthis study yas. 27-hours. Was the urine collected over a long enough time interval to obtain a good estimate of nti in motifitexcreted at infinite time? (© Does the renal clearance of precsinamide a ON treatments? % L) BARAAR 5 190 DLEBASUSE RRL HBAS RRM ees wast: 190 R 3 Ree ZR | Z, | ‘A drug follows the kinetics ofa one-compartment model and has an elimination balf-tife ‘of 3 hours. Given the apparent volume of distribution of 7L, caleulate the elimination rate when the plasma drug concentration is 2 ug/ml. (5 4) A drug with an elimination constant of 0.693 hr was given to a male patient (80 kg) by itravenous infusion ata rate of 300 mg/h. At 7 hours after infusion, the plasme drug, concentration was 11 gin. ifthe faction of unchanged drug excreted in urine is 0.8, (@) What isthe renal clearance ofthis drug. (5 8) (®) What isthe probably mechanism forthe renal excretion ofthis dug? (5-53) ‘The bioevalbiliyof propranolol is 26%, Propranolol is 87% bound to plasma proteins nd hasan lization hal if gf 9dr. fREApparent volume of isybution of Pops 43 Lg eb 0.5 otha ge creda ere Astuming the hepatic bdo oa F500 mi (a) Estimate the hepatic irdtiow ratio for propranolol (S39) (8) Provide at east io feos SE srr 6%) Both drug Aand drug Bee whom Ge The hepatic inninic clearance of tras rad flaws: |) 25 Drag A: 1500 mii Drag B: 26min Which drug is likely to be significantly influenced by the concomitant use of grapefiit 2, Why? (5 23) ‘The elimination halflife ofan antibiotic is 3 hours with an apparent volume of {distribution equivalent to 20% of body weight. The usual therapeutic range for this antibiotic is berween 5 and 15 pg/ml. Adverse toxicity for this drug is often observed at serum concentrations greater 20 ug/l. Caleulate dosage regimen (multiple TV doses) that Will maintain the serum concentration between S and 15 jig/ml for a 70-kg man. (10 4) Explain why subsequent equal doses of a drug do nat produce the same ‘Pharmacodynamic effect as the frst dose of drug, () Provide an explanation based on pharmacokinetic considerations. (5.53) (©) Provide an explanation based on pharmacodynamic considerations. (5 3) PRM SRE