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

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 (AUC 0-30 ) and peak plasma concentration (C max ) of quetiapine by 9.93% and 42.68%, respectively, while significantly increasing the exposure of norquetiapine.The curcuminoid/piperine pretreatment increased the AUC 0-30 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. RezumatScopul studiului a fost investigarea interaciunilor farmacocinetice ale curcuminei i ale unui extract de curcuminoide/piperin cu quetiapin.Aceasta este metabolizat, n principal, prin intermediul enzimei CYP3A4, iar interaciunile implicnd curcumina au artat modularea activitii enzimelor CYP.n fiecare dintre cele trei grupuri experimentale au fost alocai 13 obolani Wistar albino.Grupul de Referin a primit o doz oral de 85 mg/kg quetiapin.Primului grup test i s-a administrat quetiapin dup un pretratament de ase zile cu curcumin, iar celui de al doilea grup test dup un pretratament de ase zile cu curcuminoide i piperin.Concentraiile plasmatice ale quetiapinei i ale metabolitului su activ, norquetiapina, au fost msurate cu o metod LC-MS/MS, iar parametrii farmacocinetici au fost calculai prin analiz farmacocinetic noncompartimental.Curcumina a redus aria de sub curb (AUC 0-30 ) i concentraia plasmatic maxim (C max ) a quetiapinei cu 9,93%, respectiv 42,68%, crescnd semnificativ expunerea norquetiapinei.Pretratamentul cu curcuminoide/piperin a crescut AUC 0-30 a quetiapinei i a norquetiapinei de 1,60 i 1,78 ori comparativ cu grupul de referin.Rezultatele in vivo relev influena curcuminei simple, ct i a formulrii cu biodisponibilitate mbuntit asupra quetiapinei.Pentru administrarea concomitent n siguran a substanelor studiate, aceste interaciuni trebuie analizate n continuare n studii clinice.