Elevated clozapine plasma concentration secondary to a urinary tract infection: proposed mechanisms

A 59-year-old woman was admitted to a tertiary care refractory psychosis unit with a referral diagnosis of schizoaffective disorder. She was maintained on 400 mg of clozapine once daily as part of her pre-existing treatment for auditory hallucinations. The steady state plasma concentrations of clozapine and norclozapine were 2542 and 1465 nmol/L, respectively. Several cytokines involved in the acute inflammatory response have been identified as having an inhibitory effect on the expression of certain drug metabolizing enzymes. UTI-associated increases in the plasma concentrations of clozapine and norclozapine are most readily explained by the actions of cytokines on drug metabolism and/or protein binding. Since we could not readily order plasma concentrations of unbound clozapine or α1-acid glycoprotein, confirmation of the underlying mechanism was not possible. As such, clinicians should monitor for clozapineassociated adverse effects and adjust the dosage accordingly.