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EFFECT OF CURCUMIN AND CURCUMINOID/PIPERINE EXTRACTS ON THE PHARMACOKINETICS OF QUETIAPINE FROM IN VIVO STUDIES IN RATS

IULIA-MARIA CIOCOTIȘAN, DANA MARIA MUNTEAN *, ELENA DINTE, LAURIAN VLASE

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This pharmacokinetic study investigated the interactions of curcumin and a curcuminoid/piperine mixture with quetiapine. The CYP3A4 enzyme is the main metabolic pathway for quetiapine, while curcumin-related drug interactions have been reported to modulate CYP enzyme activity. Thirteen Wistar albino rats were assigned to each of the three experimental groups, with the reference group receiving an oral dose of 85 mg/kg quetiapine. The first test group was administered quetiapine following a six-day pretreatment with crude curcumin, whereas the second test group received quetiapine after a six-day pretreatment with a piperine bio-enhanced curcuminoid formulation. Plasma levels of quetiapine and its active metabolite, norquetiapine, were determined by LC-MS/MS, with pharmacokinetic parameters determined through non-compartmental analysis. Curcumin decreased the area under the plasma concentration-time curve (AUC0-30) and peak plasma concentration (Cmax) of quetiapine by 9.93% and 42.68%, respectively, while significantly increasing the exposure of norquetiapine. The curcuminoid/piperine pretreatment increased the AUC0-30 of quetiapine and norquetiapine by 1.60- and 1.78-fold compared to quetiapine alone. In vivo findings demonstrate that curcumin, whether crude or bio-enhanced, modified the systemic exposure to quetiapine. To ensure safety of the coadministered substances, these interactions should be further assessed in clinical settings.