Name: ____________________ UFID #: ______________________ PHA 5127 Second Exam Fall 2007 On my honor, I have neither given nor received unauthorized aid in doing this assignment. Name Put all answers on the bubble sheet TOTAL _______/130 pts 1Name: ____________________ UFID #: ______________________ Question Set I (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 as true (A) or false (B). Drug A is cleared only by hepatic metabolism and has an intrinsic clearance of 80,000 L/h Looking at intrinsic clearance you can tell this is a high extraction drug. 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 if given together. 2Name: ____________________ UFID #: ______________________ Question Set II (18 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 a peak concentration of 0.18 μg is observed (Co). When given orally, the oral bioavailability is 99.9 %. Plasma Protein Binding is 50% (fu=0.5). Peak [ug/ml] 0.18 V [L] 108 F (%) 99.9 fu0.5 Mark whether the following statements are true (A) or false (B). This drug is a low extraction drug. E=0.001 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 also responsible for metabolism of Drug A will significantly affect the clearance of Drug A 11: T F Drug B, known to induce enzymes that are also responsible for metabolism of Drug A is likely to decrease the clearance of 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 hydrophilic strong acid, protein bound drug that is only eliminated through the kidneys (some answers may be used more than once). Select the effect on kinetics (A) Oral Bioavailability F↓ (B) Clren ↓ (C) VD ↑ (D) oral bioavailability F↑ (E) nothing happens or effect is not listed “Strong acid” indicates that this drug will be mostly ionized at physiological pH. Physiological change 12: Decrease in plasma protein binding_(C)____ 13: Decrease in tissue binding _(E)___ 14: Decrease in GFR __(B)__ 15: Increase in urine flow__(E)___ 4Name: ____________________ UFID #: ______________________ Question Set IV (20 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 to that of blood (about 7). The volume of distribution is 40L. 16: What value describes best the clearance? (10 points) A: 0.15 mL/min B: 13 mL/min C: 130 mL/min D: 6.6 mL/min E: none of the above Fu=0.1 GRF*fu=13mL/min this drug has a significant portion unionized at physiological pH and therefore will undergo some reabsorption. If it were totally reabsorbed the clearance would be urine flow*fu=0.2 mL/min. However since our drug is ~50% ionized, only the uniozied half can be reabsorbed. So the clearance will be 6.5 ml/min which represents the 50% of the drug which undergoes filtration and is then trapped in the tubule (the ionized portion) plus a small amount which has the ability to be reabsorbed and is eliminated by urine flow. So the clearane will be a little bit higher than 6.5mL/min. 17: Assume a one compartment body model? What is the renal clearance of a typical aminoglycoside in a patient showing a creatinine clearance of 65 ml /min (10 points). The plasma protein binding for this aminoglycoside is 90 %. A: 58.5 ml/min B: 130 ml/min C: 65 ml/min D: 6.5 ml/min E: 35.8 ml/min Clren=GRF*Fu=65 mL/min*0.1=6.5 mL/min. Aminoglycosides do not undergo reabsorption. 5Name: ____________________ UFID #: ______________________ Question Set V (10 points) 18: 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: 70 ml/min D: 103 ml/min E: none of the above 280 lbs/2.2=127.3 kg IBW=50+2.3*10=73 kg This patient is obese must use adjusted body weight in Creatinine clearance equation. ABW=73kg+0.4*(127.3-73)=94.7kg Clcr=(140-34)*94.7kg/(72*1.5 mg/dl)=92.9 mL/min 6Name: ____________________ UFID #: ______________________ Question Set VI (5 points) 19: The following patients differ in the (A) dose received (B) clearance (C) volume of distribution Peak (mg/L) 0.60 0.60 Ke (1/h) 0.2 0.5 t1/2 (h) 2.9 1.4 AUC (mg/L*h) 2.50 1.25 00.20.40.60.80 6 12 18 24 The peak concentration is the same, which means that these patients were given the same dose and have the same Vd. Clearance must be different because the elimination rate is different. 7Name: ____________________ UFID #: ______________________ Question Set VII (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) 20: T F The renal clearance of a drug (as determined by filtration and reabsorbtion) always depends on the tissue binding of the drug. No, Protein binding. 21: T F To determine the clearance of a drug, one needs to know