NANONIZED CURCUMIN IMPROVED ORAL BIOAVAILABILITY OF BROMOCRIPTINE THROUGH CYP3A ENZYME INHIBITION IN RATS

Abstract

Curcumin (CUR) a water insoluble dietary flavonoid and is reported to inhibit CYP3A4 enzyme. The objective of present study was to assess the effect of CUR and nanonized curcumin (NC) on bromocriptine (BRO) metabolism in rats. NC was prepared by antisolvent precipitation method and was evaluated for particle size and solubility. CYP3A inhibitory activity of CUR was assessed in vitro using erythromycin-N-demethylase (EMD) assay. CYP3A inhibitory effect of CUR and NC confirmed in vivo using pharmacokinetic study of midazolam. These findings were further confirmed by an in vivo pharmacokinetic study in which BRO was administered (10 mg/kg, p.o) to CUR and NC (60 mg/kg, p.o.) pretreated (10 days) rats and its plasma concentrations were determined by HPLC analysis. CUR significantly (p less than 0.05) inhibited CYP 3A activity in EMD assay. CUR and NC significantly (p less than 0.05) increased plasma concentrations of midazolam in dexamethasone pretreated rats. In addition, in vivo studies revealed that CUR and NC pretreatments significantly (p less than 0.05) increased Cmax and AUC and decreased CL/F of BRO compared with BRO group.NC pretreatment may increase the bioavailability of BRO which could be mediated through the inhibition of CYP 3A enzymes.