Name: ____________________ UFID #: ______________________ PHA 5127 Second Exam Fall 2008 On my honor, I have neither given nor received unauthorized aid in doing this assignment. Name Put all answers on the bubble sheet TOTAL _______/ 170 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 is true (A) or false (B). Drug A is cleared only by hepatic metabolism and has an intrinsic clearance of 0.8 L/h 1: T F The oral bioavailability of this drug will be larger than 80%. 2: T F Plasma protein binding will affect the oral bioavailability of this drug. 3: T F The hepatic clearance of this drug is 1333 L/min. 4: T F Plasma protein binding will affect the hepatic clearance of this drug. 5: T F Drug B, known to induce enzymes, also responsible for metabolism of Drug A, will significantly affect the clearance of Drug A. 2Name: ____________________ UFID #: ______________________ Question Set II (25 points) True (A) or False (B). On the bubble sheet mark A for true or B for false Imagine a lipophilic unionized drug A with a volume of distribution of 108 L. When given by an iv bolus injection, the peak concentration of 0.18 µg/ml is observed (Co). When given orally, the oral bioavailability is 1.9 %. Plasma Protein Binding is 50% (fu=0.5). Peak [µg/ml] 0.18 V [L] 108 F (%) 1.9 fu 0.5 Mark whether the following statements are true (A) or false (B). 6: T F The drug is highly metabolized in the liver. 7: T F Plasma protein binding will affect the oral bioavailability of this drug. 8: T F The hepatic clearance of this drug will be smaller than the Clren. 9: T F Plasma protein binding will affect the hepatic clearance of this drug. 10: T F Drug B, known to induce enzymes that are also responsible for metabolism of Drug A, will significantly affect the clearance of Drug A. 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 acid (pKa=7.0), protein bound drug that is only eliminated through the kidneys (some answers may be used more than once). The pH of the urine is 7.0 Select the effect on kinetics (this effect should be clinically relevant) (A) ClREN ↑ (B) Clren ↓ (C) VD ↓ (D) oral bioavailability F↑ (E) nothing happens or effect is not listed Physiological change 11: Decrease in plasma protein binding_____ 12: Decrease in urine pH ____ 13: Increase in liver blood flow ____ 14: Doubling in urine flow_____ 4Name: ____________________ UFID #: ______________________ Question Set IV Total points 30 A drug is being cleared by the liver and kidneys. The drug is polar, has a molecular weight of 400 Dalton and is neither an acid nor a base. Plasma protein binding is 50% (fu=0.5). The oral bioavailability is determined by first pass and is 60%. Assume liver blood flow of 80 L/h, a GFR of 130 ml/min and a urine flow of 2 ml/min. What is the hepatic clearance expressed in L/h. Values between 1 and 80 L/h. Express as full Liters/h (50 not 50.4 L/h). (10 points) 15 Mark A, B, C, or D, if the number in the tens column is 1 (A), 2(B), 3(C), 4(D), 5(E). Leave blank if this is not the case This would be E for 50 L/h) 16: Mark A, B, C, D, E if the number in the tens column is 6 (A), 7(B), 8(C), 9(D), 0(E) Leave blank if this is not the case. You would leave this blank for 50 L/h) 17: Mark A, B, C, or D, if the number in the ones column is 1 (A), 2(B), 3(C), 4(D), 5(E). Leave blank if this is not the case . You would leave this blank for 50 L/h) 18: Mark A, B, C, or D, if the number in the ones column is 6 (A), 7(B), 8(C), 9(D), 0 (E) Leave blank if this is not the case. This would be E for 50 L/h) 5Name: ____________________ UFID #: ______________________ What is the renal clearance expressed in mL/min. Values between 0 and 90 mL/min. Express as full mL/min (50 not 50.4 mL/min). (10 points) 19: Mark A, B, C, or D, if the number in the tens column is 1 (A), 2(B), 3(C), 4(D), 5(E). Leave blank if this is not the case This would be E for 50 L/h) 20: Mark A, B, C, D, E if the number in the tens column is 6 (A), 7(B), 8(C), 9(D), 0(E) Leave blank if this is not the case. You would leave this blank for 50 L/h) 21: Mark A, B, C, or D, if the number in the ones column is 1 (A), 2(B), 3(C), 4(D), 5(E). Leave blank if this is not the case. You would leave this blank for 50 L/h) 22: Mark A, B, C, or D, if the number in the ones column is 6 (A), 7(B), 8(C), 9(D), 0 (E) Leave blank if this is not the case. This would be E for 50 L/h) 6Name: ____________________ UFID #: ______________________ What is the total clearance expressed in L/h. Values between 0 and 90 L/h. Express as full L/h (50 not 50.4 L/h). (10 points) 23: Mark A, B, C, or D, if the number in the tens column is 1 (A), 2(B), 3(C), 4(D), 5(E). Leave blank if this is not the case This would be E for 50 L/h) 24: Mark A, B, C, D, E if the number in the tens column is 6 (A), 7(B), 8(C), 9(D), 0(E) Leave blank if this is not the case. You would leave this blank for 50 L/h) 25: Mark A, B, C, or D, if the number in the ones column is 1 (A), 2(B), 3(C), 4(D), 5(E). Leave blank if this is not the case . You would leave this blank for 50 L/h) 26: Mark A, B, C, or D, if the number in the ones column is 6 (A), 7(B), 8(C), 9(D), 0 (E) Leave blank if this is not the case. This would be E for 50 L/h) 7Name: ____________________ UFID #: ______________________ Question Set V (10 points) A lipophilic acidic drug (pka of 7) is eliminated only by the kidney. Plasma protein binding is 90%. Glomerular filtration rate is normal (130 ml/min). Urine flow is 2ml/min.Urine pH is similar 7. The volume of distribution is 40L. 27: What value best describes the clearance? (5 points) A: 0.15 mL/min B: 13 mL/min C: 130 mL/min D: 6.6 mL/min 28: Assume a one compartment body model? What is the renal clearance of a typical polar, (hydrophilic) drug showing 50% plasma protein binding. The patient has a creatinine clearance of 130 ml /min (5 points). A: