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Case Study 4 PHA 5127 Fall 2006 1 A. What happens to the bioavailability of a high extraction drug when the following parameters are increased: Fu, QH, Clint As Fu and Clint increase the bioavailability decreases. As QH increases the bioavailability increases. F=QH/(Fu*Clint) B. Explain why changes in the above parameters do not change the bioavailability of a low extraction drug? With a low extraction drug we know that a large amount of drug gets into the body and avoids first pass metabolism, meaning the extraction ratio is very small. This means that the bioavailability is about 1 (F=1-E, F~1). By changing the small extraction ratio there is not much effect on bioavailability. Changing F from 99% from 98% is insignificant. 2. A patient with liver failure was given 70mg of a drug as an IV bolus injection. The plasma concentrations at 3 hours and 8 hours after injection were 1.31mg/L and 0.65mg/L respectively. The drug is eliminated by hepatic metabolism and renal excretion via glomerula filtration. The plasma protein binding for the drug is 60%... What are the hepatic clearance and the volume of distribution of this drug in this patient? (Use 130ml/min for glomerula filtration rate). ke =-ln(0.65/1.31)/(8-3)=0.14/hr C0 = 1.31*exp(0.14*3)=1.99 mg/L Vd = Dose/C0=70/1.99=35.2L Cl = ke*Vd=0.14*35.2=4.93L/hr Clren = GFR*fu=130*60*0.4/1000=3.12L/hr Clhep = 4.93-3.12=1.81L/hr 3. Mark True or False T F highly ionized substances tend to remain in the urine T F tubular reabsorption can only be an active transport process T F fluid is filtered across the glomerulus through passive diffusion 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 A drug with fu = 0.1 and a ClREN = 20 mL min-1 is Actively secretedA 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


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UF PHA 5127 - Case Study 4

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