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PHA 5127 (Fall, 2008) Case Study #4 Q1. For the following situations, indicate whether the drug is: filtered, reabsorbed, actively secreted, or reabsorbed through transporters ((Assume GFR is 130 mL min-1, urine flow is 1.5 ml min-1) a). A drug with fu = 0.02 and a ClREN = 20 mL min-1 ClREN = 20 mL > fu*GFR=2.6 mL min-1 => actively secreted b). A drug with fu = 0.40 and a ClREN = 52 mL min-1 ClREN = 52 mL min-1 = fu*GFR=52 mL min-1 => filtered c). A drug with fu = 0.60 and a ClREN = 0.9 mL min-1 ClREN = 0.9 mL min-1< fu*GFR=98 mL min-1 => reabsorbed ClREN = 0.9 mL min-1= fu*urine flow=0.9 mL min-1 => reabsorbed through passive diffusion d). A drug with fu = 1.0 and a ClREN = 0.3 mL min-1 ClREN = 0.3 mL min-1< fu*GFR=130 mL min-1 => reabsorbed ClREN = 0.3 mL min-1< fu*urine flow=1.5 mL min-1 => reabsorbed through transporters Q2. A male patient is 5 ft 10 inches tall, 40 years old, and weights 80 kg. His serum creatinine is 1.5 mg/dl. Please estimate his GFR. 50 2.3 10 7380 120%(140 40) 7368 / min72 1.5IBW kgTBW kg IBW not an obese patient use IBWGFR CrCL ml=+ •==< ⇒ ∴−•== =•Q3. Mark each of the following statements True or False. T F The maximum value of renal clearance can not excess the glomerula filtration rate. T F The renal clearance of a drug (as determined by filtration and reabsorbtion) always depends on the tissue binding of the drug. T F Drinking a lot of water (urine flow is doubled) will increase significantly the renal clearance of aminoglycocsides. T F For an acidic drug with a pka of 1.0, adjustment of the urine pH within physiological ranges will significantly change the renal clearance. T F To determine the clearance of a drug, one needs to know whether the drug is a one or two compartment drug. T F Since creatinine is endogenous and predominantly eliminated by kidney, its clearance is a good estimation of renal active secretion. T F The larger the volume of distribution, the smaller the AUC of a given drug. Q4. Define the term linear pharmacokinetics. z no saturation of binding sites (linear protein binding) z no saturation of enzymes or transporters z CL and Vd are independent of dose z AUC and Ct changed proportionally with drug dose


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