PHARMACOKINETICS OF CLOZAPINE AND RISPERIDONE - A REVIEW OF RECENT LITERATURE

The current Literature describing the pharmaco-kinetics of the atypica l antipsychotics clozapine and risperidone is reviewed, and discussion on the clinical significance of these data is presented. These drugs are well absorbed when taken orally but are poorly bioavailable becaus e of presystemic elimination. They are highly cleared by hepatic metab olism involving specific P450 isozymes. Risperidone elimination produc es a potent active metabolite. Neither of the drugs has received exten sive study related to drug-drug interactions, but several are potentia lly important because a purported therapeutic plasma concentration ran ge is proposed for clozapine and a possible curvilinear dose response relationship has been reported for risperidone. The current clinical p harmacokinetic database for these atypical antipsychotics suggests tha t much can be learned with additional study that would be of value in individualizing their dosage regimens.