NAME: _____________________________ UFID: _______________________________ PHA 5127 Second Exam Fall 2006 On my honor, I have neither given nor received unauthorized aid in doing this assignment. Name Put all answers on the bubble sheet TOTAL _______/160 pts 1NAME: _____________________________ UFID: _______________________________ Question Set I (True or False) (25 points) True (A) or False (B). On the bubble sheet mark A for true or B for false Mark whether the following statements as true or false for drug A, which is cleared only by hepatic metabolism and has a CLtot of 80 L/h 1: T F This drug is a low extraction drug 2: T F The clearance of another drug eliminated only by the kidney (only filtered not re-absorbed) will be smaller than that of Drug A 3: T F The oral bioavailability of this drug will be significantly smaller than 80% 4: T F The oral bioavailability will depend on liver blood flow 5: T F Drug C, known to induce enzymes also responsible for metabolism of Drug A will significantly affect the clearance of Drug A 2NAME: _____________________________ UFID: _______________________________ Question Set II (15 points) Imagine a high extraction drug that is only eliminated via hepatic metabolism. Two patients have been injected with the same dose of this drug. They show the following pharmacokinetic properties Cmax [μg/ml] 0.180.18Ke [1/h] 0.550.73Vd [L] 108108CL [L/h] 5680F (%) 61 6: A list of physiological parameter is shown below. Identify the one physiological parameter that would explain all differences in above pharmacokinetic parameters Parameter- A. GFR B. fu C. fut D. Qhep E Clint 3NAME: _____________________________ UFID: _______________________________ Question Set III (Matching) (20 points) For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a lipophilic, unionizable (no acid or basic group in the molecule), protein bound drug that is eliminated only through the kidneys (some answers may be used more than once). Select the effect on kinetics (A) ClREN ↑ (B) ClHEP ↓ (C) VD ↑ (D) oral bioavailability F↑ (E) factor not listed in A-D Physiological change 7: Decrease in plasma protein binding__A or C___ 8: Increase in tissue binding __C__ 9: Decrease in liver blood flow__E__ 10: Increase in urine flow__A___ Question Set IV (Matching) (20 points) (Assume GFR is 130 mL min-1, urine flow is 1.5 ml min-1) For the following situations, indicate whether the drug is: Select from the following choices: (A) filtered (B) reabsorbed (C) actively secreted (D) reabsorbed through transporters 11: A drug with fu = 0.02and a ClREN = 20 mL min-1 is _C__ 12: A drug with fu = 0.40 and a ClREN = 52 mL min-1 is _A__ 13: A drug with fu = 0.60 and a ClREN = 0.9 mL min-1 is __B_ 14: A drug with fu = 1.0 and a ClREN = 0.3 mL min-1 is _D__ 4NAME: _____________________________ UFID: _______________________________ Question Set V (10 points) A hydrophilic drug (predominantly ionized at pH=7.4) is eliminated only by the kidney. Plasma protein binding is 90%. Glomerular filtration rate is normal (130 ml/min). Urine flow is 2ml/min. No active renal secretion or active reabsorption after renal filtration is observed. The volume of distribution is 40 L. 15: What is the clearance? (10 points) A. 0.15 mL/min B. 13 mL/min C. 1 mL/min D. 130 mL/min 16: Assume a one compartment body model? What is the renal clearance of a typical aminoglycoside in a patient showing a creatinine clearance e of 65 ml /min(10 points). The plasma protein binding for this aminoglycoside is 55 %. A. 58.5 ml/min B. 130 ml/min C. 65 ml/min D. 29.3 ml/min E. 35.8 ml/min 5NAME: _____________________________ UFID: _______________________________ Question Set VI (20 points) 17: Robert is very sick and needs treatment with an aminoglycoside. In order to start him on the aminoglycoside an iv bolus loading dose shall be given. Your responsibility is to give him the first dose. In order to do so, you have to estimate Robert’s creatinine clearance. Robert is 5 ft 10 inches tall, 34 years old, male, and weights 280 pounds. His serum creatinine is 1.5 mg/dl. What creatinine clearance do you come up with? A. 72 ml/min B. 84 ml/min C. 93 ml/min D. 103 ml/min E. none of the above 6NAME: _____________________________ UFID: _______________________________ Question Set VII The same dose of Alprazolam was given either alone or with ketoconazole. Explain what is going on by selecting the correct answer from the following list. (5 points) 1: The clearance of alprazalam is increased in the presence of Ketoconazole. 2: Alprazalam is likely to be a low extraction drug. 3: Ketoconazole decreases the volume of distribution of Alprazolam, thereby increasing the half-life of the drug 4: Ketoconazole is likely to increase liver blood flow. 18. The correct answer is: __________ A. 1 B. 2 C. 3, 4 D. 2, 3 E. 1, 2, 3, 4 7NAME: _____________________________ UFID: _______________________________ Question Set VIII (True or False) (30 points) True (A) or False (B). On the bubble sheet mark A for true or B for false Mark whether the following statements are true (A) or False (B) 19: T F The renal clearance of a drug depends the tissue binding of the drug. 20: T F The half-life of a drug increases with increasing tissue binding. 21: T F To determine the clearance of a drug, one needs to know whether the drug is a one or two compartment drug. 22: T F Drinking a lot of water (urine flow is doubled) will increase the renal clearance of aminoglycosides 23: T F For an acidic drug with a pka of 2.0, adjustment of the urine pH within physiological ranges will significantly change the renal clearance. 24: T F For a drug with linear pharmacokinetics, hepatic clearance depends on the drug plasma concentration, as the rate of metabolism increases with increasing drug concentrations in the blood. Question Set IX (True or False) (15 points) True (A) or False (B). On the bubble sheet mark A for true or B for false Mark whether the following statements are true (A) or false (B). Assume linear pharmacokinetics for all questions. 25: T F The larger the volume of distribution,