Pharmacokinetics - PHAR 7633

Homework #3

Due 5^{th} November 1999

Not to be graded

1. Assuming a one compartment linear pharmacokinetic model, with kel = 0.14 hr^{-1} and V = 54 L, calculate the plasma concentration at 1, 2, 4, 6, 9, 12, 18 and 24 hours after the following IV bolus dose schedule: 400 mg at time 0 hr; 200 mg at 4 hr; 300 mg at 12 hours. Plot the data (as points) on linear and semi-log graph paper. Sketch a line reflecting the plasma concentration throughout each dosing interval. (Note: non-uniform doses and dosing interval).

2. Calculate an appropriate dosing regimen for the following male patient; age = 56 years, weight = 86 kg, serum creatinine = 1.6 mg/ 100 ml (mg %). With this drug the kel is a function of creatinine clearance; kel = 0.04 hr^{-1} with CL_{Cr} = 15 ml/min and kel = 0.14 hr^{-1} with CL_{Cr} = 60 ml/min. The apparent volume of distribution was 0.78 L/kg. Develop a dosing regimen to keep the peak concentration close to but below 6 µg/ml and the trough concentration **below** 0.5 µg/ml. Adjust tau appropriately. Round doses to the nearest/appropriate 5 mg and calculate the expected maximum and minimum plasma concentrations.

3. A drug is to be given orally every twelve hours to achieve an average concentration of 20 mg/L. Calculate the dose (F = 0.75) required if t_{1/2} = 17 hours and V = 42 L. Round your answer to the nearest 25 mg. Estimate the average, peak and trough concentrations after steady state is reached.