BRIEF COMPARISON OF THE PHARMACOKINETICS AND PHARMACODYNAMICS OF THE TRADITIONAL AND NEWER ANTIPSYCHOTIC-DRUGS

The pharmacokinetics and pharmacodynamics of chlorpromazine, haloperid ol, clozapine, and risperidone are described. Most traditional antipsy chotic drugs have similar pharmacokinetic profiles that differ from th e newer agents in several key respects. Traditional agents tend to be completely absorbed and undergo extensive presystemic elimination, but clearance tends to be almost exclusively by hepatic-enzyme metabolism . The volume of distribution is large, steady-state plasma concentrati ons are highly variable, and many traditional antipsychotic drugs have pharmacologically active metabolites. The newer antipsychotic agents clozapine and risperidone are also well absorbed and undergo extensive presystemic elimination. They are cleared mostly through hepatic-enzy me metabolism, but a small portion of risperidone is cleared renally. Steady-state plasma concentrations of clozapine and risperidone exhibi t large interpatient differences at therapeutic dosages. The primary m etabolite of risperidone, 9-hydroxyrisperidone, has activity equipoten t to that of the parent drug. It is not clear whether clozapine produc es active metabolites. Basic information on the pharmacokinetics and p harmacodynamics of clozapine and risperidone is known; however, more i nformation is needed.