DOSE-DEPENDENT PHARMACOKINETIC INTERACTION OF CLOZAPINE AND PAROXETINE IN AN EXTENSIVE METABOLIZER

A 53-year-old patient suffering from delusional disorder developed an anticholinergic syndrome 19 days after initiation of paroxetine in add ition to a steady dose of clozapine. The clozapine plasma concentratio n had doubled and was in the toxic range. On re-exposition with a lowe r clozapine dosage the increase was significantly lower. The importanc e of a dose-dependent interaction of both drugs is emphasized and a po ssible pharmacological explanation described. With regard to interacti ons of SSRIs and clozapine, fluvoxamine, a potent inhibitor of cytochr ome P4501A2, gives rise to higher clozapine levels at an earlier time, compared to other SSRIs (paroxetine, fluoxetine and sertraline), whic h are potent cytochrome P4502D6 inhibitors.