INTRODUCTION: Co-morbid medical and psychiatric conditions are common in individuals with schizophrenia. As such, selecting antipsychotic medications with a low potential for drug-drug interactions (DDIs) is crucial, as many are extensively metabolized by hepatic cytochrome P450 (CYP) isozymes. METHODS: This randomized, crossover study examined the effects of paroxetine (a potent CYP2D6 inhibitor) on the pharmacokinetic parameters of a single dose of the novel antipsychotic agent, paliperidone extended-release tablets (paliperidone ER), in healthy subjects. RESULTS: The mean C (max) and AUC of paliperidone were slightly higher and paliperidone clearance was slightly lower following co-administration of paliperidone ER with paroxetine. There was a ratio of geometric treatment means of 116.48% for AUC (infinity) [90% CI: 104.49-129.84]. However, the increase in total exposure to paliperidone was not considered clinically relevant. The incidence of adverse events was lower when subjects received the combination of paliperidone ER and paroxetine compared with paroxetine alone. DISCUSSION: Results suggest that no clinically relevant pharmacokinetic interaction occurs when paroxetine and paliperidone ER are co-administered and, therefore, initiation or discontinuation of concomitant treatment with CYP2D6-inhibiting drugs does not appear to warrant an adjustment in paliperidone ER dosage.
RCT Entities:
INTRODUCTION: Co-morbid medical and psychiatric conditions are common in individuals with schizophrenia. As such, selecting antipsychotic medications with a low potential for drug-drug interactions (DDIs) is crucial, as many are extensively metabolized by hepatic cytochrome P450 (CYP) isozymes. METHODS: This randomized, crossover study examined the effects of paroxetine (a potent CYP2D6 inhibitor) on the pharmacokinetic parameters of a single dose of the novel antipsychotic agent, paliperidone extended-release tablets (paliperidone ER), in healthy subjects. RESULTS: The mean C (max) and AUC of paliperidone were slightly higher and paliperidone clearance was slightly lower following co-administration of paliperidone ER with paroxetine. There was a ratio of geometric treatment means of 116.48% for AUC (infinity) [90% CI: 104.49-129.84]. However, the increase in total exposure to paliperidone was not considered clinically relevant. The incidence of adverse events was lower when subjects received the combination of paliperidone ER and paroxetine compared with paroxetine alone. DISCUSSION: Results suggest that no clinically relevant pharmacokinetic interaction occurs when paroxetine and paliperidone ER are co-administered and, therefore, initiation or discontinuation of concomitant treatment with CYP2D6-inhibiting drugs does not appear to warrant an adjustment in paliperidone ER dosage.
Authors: Maximilian Gahr; Markus A Kölle; Carlos Schönfeldt-Lecuona; Peter Lepping; Roland W Freudenmann Journal: Drug Des Devel Ther Date: 2011-03-11 Impact factor: 4.162