PHA 5127

Designing A Dosing Regimen

Answers provided by

Jeffrey Stark

Mr. JM is to be started on aminophylline for the treatment of asthma. He is a non-smoker and weighs 60 kg. Design an oral dosing regimen for this patient such that the theophylline plasma levels are within the therapeutic window. Assume very fast absorption of the tablet. The following information is provided:

 

F(bioavailability) = 1 Aminophylline is 85% theophylline by weight

Vd = 0.5 L/kg 100 mg aminophylline tablets are available

Cl = 40 ml/hr/kg therapeutic window is 10-20 mg/L

 

1) Determine Vd and Cl for this patient based on the normal values given above. Calculate ke.

2) Determine the dosing interval using the relationship between t and the fluctuation factor F. The dosing interval should be practical (i.e. some factor of a 24-hour period).

3) Use the average steady-state equation to determine the dose. Note that only 100 mg tablets of aminophylline are available here.

4) Calculate the steady-state peak and trough levels based on this dosing regimen to verify that the theophylline levels are within the therapeutic range.

5) What information is needed to better design a dosing regimen for this patient?

6) How many doses will it take to reach steady-state plasma levels? If the dose or the dosing interval is changed, how long will it take to again reach the steady-state?

7) Suggest a loading dose to decrease the amount of time required to reach a therapeutic level. What would be the peak concentration after this loading dose?

Working through this problem should help you understand where many of the equations we have seen come into play.

PDF formatted File for Printing Answer