Validation of a population pharmacokinetic/ pharmacodynamic model for 5 alpha-reductase inhibitors

A population pharmacokinetic/dynamic model describing the conversion of tes tosterone to dihydrotestosterone (DHT) by 5 alpha-reductases and the irreve rsible inhibition of 5 alpha-reductase(s) by finasteride and dutasteride wa s validated. The model had been developed using data from a single dose stu dy in healthy volunteers and was validated against data from a 28-day repea t dose study in patients with benign prostatic hyperplasia. Validation was carried out by comparing results of Monte Carlo simulations to the observed data, fitting the model to the repeat dose data and comparing with previou sly derived parameter values, and examining individual predictions of the m odel for the individuals in the repeat dose study for any bias. Simulations closely predicted the outcome of the repeat dose study, estimated paramete rs of the pharmacodynamic modelling were generally close to within 88 to 11 6% of those from the original model and the individual predictions did not indicate any bias. Thus the model derived from single dose data from health y volunteers was considered to be valid for the prediction of DHT levels in the patient population after repeated dosing of dutasteride and finasterid e. (C) 1999 Published by Elsevier Science B.V. All rights reserved.