Olanzapine metabolizing enzymes

Recall that one of the key drug-metabolizing enzymes is the cytochrome P450 (CYP450) enzyme called 1A2. Two atypical antipsychotic drugs are substrates of 1A2, namely olanzapine and clozapine. That means that when they are given con-... 

Olanzapine is metabolized by several pathways and is therefore unlikely to be affected by concurrent administration of other medications. Because olanzapine does not appear to inhibit any cytochrome P450 enzymes, it should not increase the availability of other medications through inhibition of such enzymes. Additive pharmacodynamic effects are expected if olanzapine is combined with medications that also have anticholinergic, antihistaminic, or aj-adrenergic side effects. 

Carbamazepinewasfound to decrease the plasma levels of phenothiazines by as much as 50% (described with chlorpromazine, perphenazine, and fluphenazine). It has been reported to decrease the serum levels of clozapine by about60-85% due to its hepatic cytochrome P450 (CYP) enzyme-inducing properties. Loxapine may induce carbamazepine metabolism. Carbamazepine has been shown to reduce the plasma levels of risperidone by as much as 50%, while it increases olanzapine clearance by 44% and reduces its half-life by 20%. Carbamazepine increases aripiprazole metabolism through CYP3A4 induction. Thus, the aripiprazoie dose should be doubled. 

A signifieant reduction in olanzapine plasma levels of between 32.3% and 78.8% was found in 4 patients who were additionally given valproate, thought to be due to the valproate indueing the enzymes involved in the metabolism of olanzapine. ... 

A randomised, crossover study in 9 healthy men given single doses of olanzapine 5 mg and imipramine 75 mg found no clinically relevant pharmacokinetic or pharmacodynamic interactions between the two drugs. This would seem to confirm in vitro studies using human liver mi-crosomes, which demonstrated that olanzapine causes minimal inhibition of the cytochrome P450 isoenzyme CYP2D6, an enzyme involved in the metabolism of the tricyclic antidepressants. However, one case report describes seizures, thought to be caused by the additive effects of olanzapine... 

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