UF PHA 5127 - Answers Case Study 2 (2 pages)

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Answers Case Study 2



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Answers Case Study 2

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Pages:
2
School:
University of Florida-Gainesville
Course:
Pha 5127 - Basic Principles of Dose Optimization I

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Answers Case Study 2 PHA 5127 Fall 2005 Question 1 An 50 year old male patient was admitted to hospital with gram negative pneumonia infection and was given an iv bolus of drug X 200 mg The drug concentrations at 2hr and 12hr after initial dose were reported as 7 1mg L and 1 3mg L Assuming the drug follows one compartment body model with first order elimination please calculate the total Cl AUC 0 Vd t 1 2 for drug X Answer ke ln C 2 C1 t1 t2 ln 1 3 7 1 2 12 1 7 10 0 17 hr t 1 2 0 693 0 17 4 1hr drug concentration at time zero C0 C1 exp ke t 7 1 exp 0 17 2 10mg L vd Dose C0 200 10 20 L Cl ke Vd 0 17 20 3 4 L hr AUC 0 Dose Cl 200 3 4 58 8 mg hr L Question 2 70 90 of quinidine is bound to plasma albumin and alpha 1 acid glycoprotein 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 80 for normal patients a tissue volume of 38 L and the fraction unbound in tissue 80 to calculate the volume of distribution in patients with liver disease Answer Vd Vp Vt fu fu T For patients with liver disease only fu increase all the other factors remain unchanged as we can see from the equation the Vd will increase 0 8 0 8 0 64 fu 1 0 64 0 36 normal patients 20 free fraction Vd 3 38 0 36 0 8 20 1 L Question 3 Researchers recently found out that grape fruit juice is CYP3A4 inhibitor When taking together with grape fruit juice the intrinsic hepatic clearance CL int of drug B is decreased by 20 Main pharmacokinetic parameters of drug B were listed as following Hepatic clearance WITHOUT taking grape fruit juice CL hep 10 L hr Fraction unbound fu 0 4 Please calculate what is the new hepatic clearance when drug B is taking together with grape fruit juice Assume the hepatic blood flow is 90 L hr Answer First calculate the original CL int CL QH fu CLint QH fu CLint CL 90 0 4 CLint 90 0 4 CLint 10 CLint 28 125 28 1 L hr Then calculate the new CL hep CL QH fu CLint



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