Name: ____________________ UFID#: ______________________ PHA 5127 First Exam Fall 2003 On my honor, I have neither given nor received unauthorized aid in doing this assignment. KEY Name Question/Points 1. ________/14 pts 2. ________/6 pts 3. ________/15 pts 4. ________/12 pts 5. ________/20 pts 6. ________/10pts 7. ________/10pts 8. ________/12pts 9. ________/10pts 10. ________/16pts TOTAL _______/125 pts 1Name: ____________________ UFID#: ______________________ 1. List the wrong statements. A drug shows a plasma protein binding of 50% and a volume of distribution of 100 L. The intrinsic clearance of this drug in the liver is much smaller than the liver blood flow. The oral bioavailability of this drug: (14 points) A will be 50%. B will highly depend on liver blood flow. C will be very small (< 10%). D will be affected by the GFR. E will be significantly increased if the tissue binding is increased. F will be significantly increased if the plasma protein binding is increased. G will be significantly increased if the intrinsic clearance is increased. The wrong statement(s) is (are): A, B, C, D, E, F, G 2Name: ____________________ UFID#: ______________________ 2. Compare the following two concentration-time profiles after a single bolus injection. The two lines differ in only one of the subsequent parameters (Vd, Dose, clearance). Please circle the parameter they differ in (6 points). 00.10.20.30.40.50.60.70102030 The 2 lines differ in Dose Vd Clearance 3Name: ____________________ UFID#: ______________________ 3. For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a lipophilic, neutral (no acid or basic group in the molecule), protein bound, low extraction drug that is also eliminated by renal elimination (some answers may be used more than once). (15 points) Write your selection (a, b, c, d, e, f, or g) on the line behind the physiological change. Physiological change Induced changes on kinetic parameters 1.) Increase in metabolic enzymes__b___ a. ClREN ↓ 2.) Decrease in urine flow__a__ b. ClHEP ↑ 3.) Increase in liver blood flow__g__ c. oral bioavailability ↓ 4.) Decrease in number of fat cells__f___ d. VD ↑ 5.) Increase in plasma protein binding _a or f__ e. oral bioavailability F↑ f. VD ↓ g. none of the above 4Name: ____________________ UFID#: ______________________ 4. For the following situations, indicate whether the drug is filtered, reabsorbed or actively secreted (Assume GFR is 130 mL min-1, urine flow is 1.5 ml min-1) (12 points) • A drug with fu = 0.02and a ClREN = 20 mL min-1 is _Actively secreted__ • A drug with fu = 0.40 and a ClREN = 52 mL min-1 is __filtered_____________ • A drug with fu = 0.30 and a ClREN = 0.45 mL min-1 is _"fully" reabsorbed/reabsorbed 5Name: ____________________ UFID#: ______________________ 5. A drug is eliminated through glomerular filtration and hepatic metabolism (no other clearance mechanisms are observed). The drug has a plasma protein binding of 50%. Glomerular filtration rate in the patient of interest is normal (130 ml/min). The drug is highly ionized, but not subject to active transport. The volume of distribution is 50 L. When given as an i.v. bolus, plasma concentrations two hour after administration were 5.2 mg/L. Four hours after administration the concentration was 2.6 mg/L. (25 pts) 5a. What is the ke? Provide full calculations and circle correct answer. Correct answer is only granted if you show calculations? t1/2 = 2 h 12/135.022ln2ln−=== htke or 135.026.22.5ln−== hhke Answer: Circle the correct answer 0.15 h-1 0.25 h-1 0.3 h-1 0.35 h-1 0.4 h-1 0.45 h-1 0.5 h-1 0.55 h-1 0.6h-1 0.65 h-1 0.7h-1 0.85 h-1 0.9 h-1 1 h-1 1.1 h-1 1.2 h-1 12h-1 120 h-1 6Name: ____________________ UFID#: ______________________ 5b. What is the total clearance of the drug. Provide full calculations and circle estimate closest to your answer from the list below. Correct answer is only granted if you show full calculations. CL = ke • Vd = 0.35 • 50 L/h Answer: 0.1L/h 0.2L/h 0.4 L/h 0.61L/h 0.8 L/h 1 L/h 3L/h 5L/h 7L/h 9 L/h 11L/h 13L/h 15 L/h 17L/h 21L/h 24L/h 27L/h 30L/h 33L/h 40L/h 45L/h 50L/h 55L/h 60L/h 65L/h 70L/h 80L/h 90L/h 100L/h 150L/h 7Name: ____________________ UFID#: ______________________ 5c. What is the renal clearance of the drug? Circle the answer closest to your estimate from the list below. Clren = GFR • fu = 130 • 0.5 = 65 ml/min = 3.9 L/h Answer: Circle the correct answer 0.1 L/h 0.2 L/h 0.3 L/h 0.4 L/h 0.5 L/h 0.7 L/h 1L/h 2L/h 3 L/h 4 L/h 6L/h 9L/h 12L/h 15l/h 18L/h 21L/h 24L/h 27L/h 30L/h 33L/h 40L/h 45L/h 50L/h 55L/h 60L/h 65L/h 70L/h 80L/h 90L/h 100L/h 150L/h 8Name: ____________________ UFID#: ______________________ 5d. What is the hepatic clearance of the drug? ? Circle the answer closest to your estimate from the list below. Clhep = ClTOT – Clren = 17 – 4 = 13 L/h Answer: Circle the correct answer 0.1 L/h 0.2 L/h 0.3 L/h 0.4 L/h 0.5L/h 0.6L/h 0.7 L/h 0.8L/h 0.9L/h 1.0L/h 1.0 L/h 1.2 L/h 1.4 L/h 1.6 L/h 1.8L 2.0L/h 2.2 L/h 2.4L/h 2.8L/h 3.0L/h 3.1 L/h 3.3 L/h 3.5 L/h 3.7 L/h 3.9 L/h 4.1 L/h 4.3 L/h 4.5 L/h 4.7 L/h 5 L/h 7 L/h 9 L/h 10 L/h 12L/h 14L/h 18 L/h 22L/h 26 L/h 30L/h 40L/h 9Name: ____________________ UFID#: ______________________ 6. The same dose of Alprazolam was given either with placebo or with carbamazepine. Briefly explain what is going on, in 5 words or less. (10 points) Please answer in 2 words or less. Enzyme induction Or Similar statement Increase in clearance and shorter half-life, more metabolism was not sufficient. 10Name: ____________________ UFID#: ______________________ 7.) Which of the following statements about renal clearance is (are) wrong? (10 points) A) The degree of tubular reabsorption might be affected by the pH of the urine. B) Highly ionized drugs with no affinity to transporters tend to stay in the urine. C) Tubular reabsorption can only be an active process. D) The renal clearance of serum creatinine is identical the GFR. E) Creatine clearance can only be used to estimate the renal clearance