Evaluation of three dosing models for the prediction of steady-state trough clozapine concentrations

Objective Therapeutic drug monitoring of clozapine may be useful for the clinical management of schizophrenic patients treated with this atypical antipsychotic drug. The aim of our study was the evaluation of three models for the prediction of steady-state trough clozapine concentration. Patients and methods The trough serum concentrations of clozapine and norclozapine were determined by high-performance liquid chromatography in 296 samples from a group of 21 schizophrenic patients selected for their good therapeutic compliance. Also, the predicted clozapine concentrations were estimated by applying the models of Oyewumi et al. (Ther Drug Monit 1995; 17: 137), Perry et al. (Biol Psychiatry 1998; 44: 733) and Rostami-Hodjegan et al. (J Clin Psychopharmacol 2004; 24: 70). Results The efficiency for the accurate estimation of clozapine concentrations as subtherapeutic (< 240 ng/mL), therapeutic (240–750 ng/mL) or supratherapeutic (> 750 ng/mL), using the models of Oyewumi et al., Perry et al., and Rostami-Hodjegan et al., was 82%, 71% and 77% respectively. Conclusions The predictive model of Oyewumi et al., which shows an easy calculation way and the greater diagnostic efficiency, may be of clinical value for the prediction of clozapine concentration or the dose required to achieve a specified concentration.