PHA 5127 First 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 _______/125 pts Equations/Useful_pharmacokinetic_equ_5127 1Question Set I (True or False) (15 points) True (A) or False (B). On the bubble sheet mark A for true or B for false A drug that does not bind to plasma proteins and tissue components has a Vd of 41 L 1.) T F The drug is likely to be hydrophilic 2.) T F VT is likely to be round 18 L 3.) T F The relatively small Vd of 41 L suggests that the hepatic clearance has to be pronounced. 4.) T F At equilibrium, the free drug concentrations in plasma and tissue will be identical. 5.) T F At equilibrium, the total blood concentrations in plasma and tissue will be identical. Equations/Useful_pharmacokinetic_equ_5127 2Question Set II (10 points) Imagine a drug that is given as an intravenous bolus. The dose was 80 mg. The elimination follows first order principles. 2 hours after administration the drug a concentration C1 of 1.48 µg/ml is observed. Four hours after the administration the concentration C2 was 0.74 µg/ml 6.) What is the elimination rate constant of this drug? (10 points) A) 0.346 h-1 B) 0.693 h C) 0.693 h-1 D) 0.346 µg/(ml*h) E) 0.370 h-1 7.) What will the concentration be 8 hours after injection? (10 points) A) 0.370 µg/ml B) 0.370 mg/ml C) 0 µg/ml D) 0.185 µg/ml E) none of the above Equations/Useful_pharmacokinetic_equ_5127 3Question Set II (continued) Imagine a drug that is given as an intravenous bolus. The dose was 80 mg. The elimination follows first order principles. 2 hours after administration the drug a concentration C1 of 1.48 µg/ml is observed. Four hours after the administration the concentration C2 was 0.74 µg/ml 8.) What is the concentration best describing the concentration directly after injection of the drug. (10 points) A) 2 µg/ml B) 3 µg/ml C) 4 µg/ml D) 5 µg/ml E) none of the above 9.) What is the half-life of this drug? (10 points) A) 1.0 h B) 1.3 h C) 3.0 h D) 4.0 h E) none of the above Equations/Useful_pharmacokinetic_equ_5127 4Question Set III 10.) A patient with renal dysfunction received a dose of vancomycin (first order elimination). Plasma concentrations were 22 and 15 mg/L at 24 and 48 hours after drug administration. Plot these two plasma concentrations on semilog paper and determine how many hours after drug administration the concentration would reach 10 mg/L (10 points) A. 2 days B. 3 days C. 4 days D. 5 days E. None of the above 11.) Calculate the area under the concentration time profile observed in the last question during day 2. (11 points) A. 220 mg*hours/Liters B. 330 mg*hours/Liters C. 440 mg*hours/Liters D. 670 mg*hours/Liters E. None of the above. Equations/Useful_pharmacokinetic_equ_5127 5Question Set IV( points) Mark the correct statements? (16 points) True (A) or False (B). On the bubble sheet mark A for true or B for false 12.) T F The volume of distribution relates the amount of drug in the body to the amount of drug in the plasma 13.) T F The volume of distribution relates the amount of drug in the body to the concentration of drug in the plasma 14.) T F The volume of distribution relates the concentration of drug in the body to the concentration of drug in the plasma 15.) T F The larger the volume of distribution, the smaller the dose necessary to achieve a certain starting concentration. Equations/Useful_pharmacokinetic_equ_5127 6Question Set V (Matching) (16 points) For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a lipophilic, acid (pka), protein bound drug Select the effect on kinetics A) VD ↑ B) VD ↓ C) decreased rate of uptake into liver tissue D) increased rate of uptake into liver tissue E) none of the above Physiological change 16.) Decrease in pH of the blood_A,D,E_ 17.) Increase in tissue binding _A_ 18.) Decrease in liver blood flow__C,E__ 19.) Decreased blood flow through poorly perfused tissues (e.g. fat tissue) _E____ Equations/Useful_pharmacokinetic_equ_5127 7Question Set VI (Select the most correct combination) 20.) What of the following drug properties is beneficial for efficient distribution into poorly perfused organs (8 points) a) The neutral (uncharged) species of a weak acid that is highly lipophilic. b) The drug is uncharged at all times and highly hydrophilic c) A strong base whose uncharged form is lipophilic d) An uncharged drug with a small octanol/water partition coefficient e) An acid with a pka of 7.4 and a large partition coefficient. A) a, c, d B) c, d, e C) a,c,e D) a, e E) none of the above Equations/Useful_pharmacokinetic_equ_5127 8Question Set VII (True or False) (9 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) for a drug that is distributed through permeability limited processes. 21.) T F Lipophilic unionized drugs are likely to enter tissues relatively fast. 22.) T F The uptake of a hydrophilic drug into tissue can be increased significantly by increasing the blood flow through the tissue 23.) T F Tissues with low blood flow should take up lipophilic unionized drugs the best. Equations/Useful_pharmacokinetic_equ_5127 9Useful Pharmacokinetic Equations Symbols D = dose  = dosing interval CL = clearance Vd = volume of distribution ke = elimination rate constant ka = absorption rate constant F = fraction absorbed (bioavailability) K0 = infusion rate T = duration of infusion C = plasma concentration General Elimination rate constant ()()kCLVdCCttCCtte==⎛⎝⎜⎞⎠⎟−=−−lnln ln12211221 Half-life tVdCL k kee120 693 2 0 693/.ln().=⋅== Intravenous bolus Initial concentration CDVd0= Plasma concentration (single dose) CCekte=⋅−⋅0 Plasma concentration (multiple dose) ()CCeektkee=⋅−−⋅−⋅01τ Peak (multiple dose) ()CCekemax=−−⋅01τ Trough (multiple dose) ()CCeekkeemin=⋅−−⋅−⋅01ττ Average concentration (steady state) CpDCLss=⋅τ Oral administration Plasma concentration (single dose) ()()CFDkVd k keeaaekt ktea=⋅⋅−⋅−−⋅ −⋅ Time of maximum concentration (single dose)