How accurate is the determination of the relative bioavailability of transdermal drug formulations from pharmacodynamic response data?
The relative bioavailability of transdermal drug formulations may be quantified by measurement of the pharmacodynamic response. Parameters such as the latency time of onset and the duration of the response may be used to obtain dose-response curves. The horizontal distance between the parallel sections of a standard and a test curve is a measure of the relative bioavailability. High penetration rate constants often lead to an insufficient parallelism of the dose-response curves because of drug depletion in the vehicle. Drug depletion may be simulated with Fick's First Law and with the Bateman equation which allows the calculation of dose-response curves for both response parameters. The simulated curves for the parameter duration are not parallel to each other and the calculated bioavailability factors do not reach the theoretical values. In contrast, the curves obtained with the response parameter 1/latency time show a sufficient parallelism at high response levels and provide accurate bioavailability data in this curve area.
Dept. of Pharm. Technol., Heinrich Heine University, Düsseldorf, Germany. leopold@uni-duesseldorf.de
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D000279:Administration, Cutaneous; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009824:Ointments; D010599:Pharmacokinetics; D015203:Reproducibility of Results
D009824:Ointments