Clozapine is a substrate for many CYP450 isozymes, in particular 1A2, 2D6, and
3A4. The risk of metabolic interactions caused by an effect on an individual
isoform is therefore minimized. Nevertheless, caution should be used in patients
receiving concomitant treatment with other drugs that are either inhibitors or
inducers of these enzymes. …
It is well recognized that most medications exhibit wide interpatient
variability in their efficacy and toxicity. For many medications, these
interindividual differences are due in part to polymorphisms in genes encoding
drug metabolizing enzymes, drug transporters, and/or drug targets (e.g.,
receptors, enzymes). …
some differences in drug efficacy response, and some toxicities, are based on
variability in exposure or in pharmacodynamic response, caused by genetic
differences …
The polymorphic forms of the CYP450s are responsible for the
development of a significant number of adverse drug reactions and may
also contribute to drug response. …