POPULATION PHARMACOKINETICS AND PHARMACODYNAMICS - POTENTIAL USE FOR GATHERING DOSE-CONCENTRATION-RESPONSE

The population approach is a general term covering different aspects o f kinetic and dynamic data collected mainly from drug-treated patients and new techniques allowing evaluation of sparse observations from ea ch subject. Such data originate from clinically relevant conditions an d can give information on several qualities of a drug. An example is g iven with the tricyclic antidepressant nortriptyline for which the kin etics and the concentration-effect relationship have been thoroughly d ocumented previously with conventional techniques. We have evaluated r etrospective data from a therapeutic drug monitoring service using a n onparametric population kinetic method (NPML) that allows description of kinetic outliers and nonlinear relationships between kinetic parame ters and covariates. In addition, drug interactions, nonlinear kinetic s and dosing habits were studied with other techniques corroborating p revious results and adding new information. The concentration-effect r elationship could not be evaluated from our data as information on eff icacy and adverse effects was of too low quality. However, several con trolled studies have defined a therapeutic concentration interval and a discussion on dosing strategies is based on this interval. Collectio n of sparse data in patients during phases II-IV of drug development a s a complement to conventional studies is highly recommendable.