PHA 5127 – Fall 2006 Answers Case Study #2 #1 Please fill in the missing numbers! Total Body Water Extracellular Fluid Intracellular Fluid Plasma Water Interstitial Fluid 41L18L 23L 3L 15L #2: The volume of distribution (Vd) of a lipophilic drug A is 800L. Answer the following questions with true or false! a) Drug A is able to cross membranes TRUE b) Drug A does not show any tissue protein binding FALSE c) Plasma protein binding is more pronounced than tissue binding FALSE d) Vd indicates that this drug is highly metabolized in the tissue FALSE e) Drug A does not leave the plasma FALSE f) Vd does reflect a real volume FALSE #3: Basics and Background of Vd. a) Give a definition of the Volume of distribution in your own words and give additionally the formula used for calculations. The volume of distribution (Vd) relates the amount of drug in the body to plasma or serum concentrations. ionconcentratPlasmabodytheinAmountVd=b) Patient H. was given 100mg of drug M intravenously. His plasma levels are listed below. Please calculate Vd! Time (h) Cp (μg/L) 1.5 171 4 119 6 79.5 7.5 51 10 1 Graphing the data on a linear scale gives a straight line. That means that drug M follows a zero order elimination process in which the same amount of drug M is eliminated per time unit. Exemplary calculation of the decrease in concentration: C(4h)-C(6h)=(119-79.5)μg/L=39.5μg/L in 2 hours That means that the plasma concentration drops approximately 20μg/L per hour. Back-extrapolation to time zero gives us a C0 of 200μg/L = 0.2mg/L. LLmgmgionconcentratPlasmabodytheinAmountVd5002.0100=== #4: Drug C has a plasma protein binding, ranging from 70-90%. In patients with chronic liver disease plasma protein binding is decreased by 20%. How will the volume of distribution change? Use a plasma volume of 3 L and the fraction bound in plasma 85% (for normal patients), a tissue volume of 38 L and the fraction unbound in tissue 30% to calculate the volume of distribution in patients with liver disease. Answer: TTpdfufuVVV+= For normal patients: LLLVd223.015.0383 =+= For patients with liver disease: Plasma protein binding decreases by 20%, all the other parameters remain the same Æ new fraction bound: 0.85 * (1-0.20) = 0.85 * 0.8 = 0.68Æ fraction unbound for liver patients: fu = 1-0.68= 0.32 (> normal patients’) LLLVd5.433.032.0383
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