Homework 2
PHA 5127 Fall 2005
Two failing pharmacy students were given 200mg IV bolus of the drug Studiehelp. The
C0 for patient A was 2.5mg/L and for patient B was 1.5mg/L. The clearance for both
patients is 5L/h. The drug is 60% bound to plasma proteins. The drug follows a one-
compartment body model, crosses membranes easily, distributes well into all tissues, and
is solely eliminated by hepatic metabolism. Assume liver blood flow is 90L/h, tissue
volume is 38L and plasma volume of 3L.
Questions:
1. Provide a quantitative explanation of why both patients have different initial
plasma concentrations (consider distribution and binding properties).
2. Calculate the half-lives for each patient. At what point in time are their plasma
concentrations the same?
3. Calculate the intrinsic hepatic clearance of the drug and the extraction ratio. Is
this a high or low extraction drug?
4. The drug Passureclas is co-administered to patient A, which competes for plasma
protein binding sites with Studiehelp (does not affect tissue protein binding),
thereby increasing the free fraction in the plasma of Studiehelp two-fold. What is
the new AUC and half-life of Studiehelp? Are they different from before?
5. Mark whether the following statements for a high extraction drug are True or
False
T F The oral bioavailability(F) will be close to 1.
T F Clearance will increase significantly after induction of the relevant enzyme.
T F Increase in plasma protein binding will decrease the extraction ratio E.
T F The hepatocyte membranes do not represent a barrier.
T F If the hepatic blood flow is reduced, the clearance will be decreased.