Quercetin nanoparticles alter pharmacokinetics of bromocriptine, reflecting its enhanced inhibitory action on liver and intestinal CYP 3A enzymes in rats

Abstract

1. Quercetin is a dietary flavonoid has extremely low water solubility and found to possess CYP3A inhibitory activity. The purpose of the present study was to evaluate the effect of quercetin and quercetin nanoparticles (NQC) on the pharmacokinetics of bromocriptine (BRO) in rats.

2. NQC prepared by antisolvent precipitation method and characterized by SEM and dissolution test. The following methods were used in this study i.e. in vitro liver and intestinal CYP3A microsomal activity and in vitro non-everted sac method. To confirm these findings, an in vivo pharmacokinetic study was also performed.

3. The results indicate that quercetin significantly (p < 0.05) inhibited the CYP3A activity in liver and intestinal microsomes. In non-everted sac study, the intestinal transport and P_app of BRO were significantly increased in NQC and quercetin groups. Furthermore, in vivo study revealed that the increased levels of C_max and AUC were comparatively high in NQC pretreated group than quercetin group. In addition, pretreatment with quercetin and NQC significantly (p < 0.05) decreased the mean CL/F and Vd/F of BRO.

4. NQC pretreatment might be result in higher plasma levels of quercetin that could inhibit the CYP3A enzyme and enhanced the bioavailability of BRO.

Keywords:

• Bioavailability
• bromocriptine
• CYP3A
• quercetin

Acknowledgements

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. University College of pharmaceutical sciences, Kakatiya University, support for the routine reagents, and permission to animal holding for this research. Authors would like to thank Inga laboratories Pvt. Ltd., Maharashtra, for providing bromocriptine as a gift sample.

Declaration of interest

The authors declare that there are no conflicts of interest.