The influence of multiple-dose oxcarbazepine on the metabolism of single-dose quetiapine. In vivo experiment in rats

Objective: Psychiatric and neurologic disorders are susceptible to polypharmacy having a higher risk of developing drug-drug interactions. Quetiapine, a frequently used atypical antipsychotic, is extensively metabolized by cytochrome P450 3A4 isoenzyme, while oxcarbazepine, an antiepileptic drug, analog of carbamazepine, is a mild-to-moderate inducer of the same isoenzyme. This study aimed to evaluate the pharmacokinetic interaction between a single dose of quetiapine and multiple doses of oxcarbazepine, as pretreatment, compared to quetiapine single-dose alone in rats.
Methods: The in vivo experiment was carried out on two groups consisting of 12 Wistar albino rats each. The control group was given a single oral dose of quetiapine 85 mg/kg. The test group received oxcarbazepine 80 mg/kg/day orally, for 5 days followed by a single dose of quetiapine 85 mg/kg. A validated liquid chromatography with tandem mass spectrometry method was employed to simultaneously measure the plasma concentrations of quetiapine and its active metabolite, norquetiapine. Non-compartmental analysis was used to determine the pharmacokinetic parameters of both quetiapine and norquetiapine.
Results: Short-term administration of oxcarbazepine determined a significant increase in the systemic exposure of norquetiapine by increasing its peak plasma concentration and the total area under the concentration-time curve by 88.85% and 5.29-fold. The expected enzyme-inducing properties of oxcarbazepine were not visible on the quetiapine’s pharmacokinetic profile, producing, although statistically insignificant, an increase in its exposure.
Conclusions: The present experiment showed that the administration of oxcarbazepine can determine some changes in the pharmacokinetics of quetiapine and norquetiapine in vivo.