Pharmacokinetics, Metabolism, and Drug-Drug Interactions of Atypical Antipsychotics in Special Populations

An awareness of the cytochrome P450 (CYP) system of primarily hepatic enzymes is crucial to managing the potential for drug-drug interactions involving the atypical antipsychotics. A coadministered drug may inhibit an enzyme that metabolizes the prescribed antipsychotic, or, conversely, a coadministered drug may induce the action of that enzyme. The result of inhibition is a higher plasma level of antipsychotic, which can cause adverse effects, while the result of induction is a lower plasma level of antipsychotic, which can compromise therapeutic efficacy. In addition, younger people tend to metabolize drugs faster than older people, men faster than women, and, for some antipsychotics (clozapine and olanzapine), those who smoke cigarettes faster than those who do not. Comorbid medical conditions and gene polymorphism may also affect drug metabolism. At times, altered CYP enzyme activity may require increasing or decreasing the dose of antipsychotic. Dose reductions in vulnerable populations (such as the elderly) are especially necessary when 2 or more factors affecting plasma clearance are present.