Long-term therapeutic drug monitoring of clozapine and metabolites in psychiatric in- and outpatients

摘要: Rationale: Clozapine is a unique antipsychotic drug, outstanding for its lack of extrapyramidal side-effects and superior efficacy in refractory schizophrenia. However, an unambiguous concentration-response relationship has not yet been established. Objective: We investigated serum concentrations clozapine, norclozapine clozapine-N-oxide psychiatric in- outpatients to identify particular metabolic patterns clozapine responders non-responders putative threshold levels response. Methods: Psychiatric assessments, CYP2D6 genotype, weekly were obtained 34 adult schizophrenic in-and (18 men, 16 women) during 10 weeks treatment with naturalistic dose design. Results: Responders (n=21) displayed significantly lower corrected compared (n=13; P<0.05), while none the other parameters (absolute concentration, metabolite ratios, gender) different. Smokers had dose-corrected concentrations. A positive correlation was observed between age average steady state Conclusions: These findings indicate possible link CYP activity response that mediated through differences No clinically meaningful pattern could be identified differentiates from non-responders. Thus, TDM seems ineffective predicting clinical Smoking behavior major determinant clearance genotype does impact disposition.