Active metabolites of neuroleptic drugs: possible contribution to therapeutic and toxic effects.

Recent studies demonstrating a relationship between plasma levels and effects of haloperidol, thioridazine, chlorpromazine, butaperazine, fluphenazine, and perphenazine suggest that therapeutic plasma level monitoring of neuroleptics may be clinically useful. Chlorpromazine, thioridazine, levomepromazine, and loxapine have active metabolites which attain plasma levels within the same range as that of the parent compound after therapeutic doses of the drug. The metabolites often have pharmacological profiles which are different from that of the parent drug, and some metabolites apparently contribute to the side effects of the drug but do not possess any neuroleptic potency. The ratios between the plasma levels of metabolites and the parent compound show large interpatient variations, and the metabolites should, therefore, be measured together with the parent drug by therapeutic plasma level monitoring. Accordingly, the assay method should be carefully selected in order to include metabolites which may contribute to the therapeutic or side effects of the drug.