New antipsychotic agents for schizophrenia: pharmacokinetics and metabolism update.

The so-called atypical antipsychotics undergo extensive metabolism, except for amisulpride, which is substantially excreted unchanged. Risperidone is oxidized by CYP2D6/CYP3A4 and iloperidone is reduced by cytosolic enzymes, although CYP1A2, CYP2E1 and CYP3A4 are involved as well. Olanzapine is both conjugated and oxidized (mainly by CYP1A2), while quetiapine and zotepine primarily undergo CYP3A4-mediated oxidation. Ziprasidone pathways include aldehyde oxidase-mediated reduction and CYP3A4-mediated oxidation. The main metabolites of risperidone, zotepine and possibly perospirone and ziprasidone contribute to the parent drug's effect. Information is limited, however, on some promising antipsychotics in the pipeline.