Prasad Neerati1, Suresh Palle2
1Department of Pharmacology, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Telangana, India.
2Department of Toxicology DMPK and Clinical Pharmacology Division, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Telangana, India.
Background: Resveratrol (RSV) is a polyphenol belonging to phytoalexin family and has been reported to show inhibitory effects on CYP3A4 enzymes. However, there has been no report about the pharmacokinetic interaction of bromocriptine (BRO) with RSV and RSV nanoparticles (NRSV) in rats. Hence, the present study was undertaken in an attempt to enhance the oral bioavailability of BRO when BRO was pretreated with RSV and NRSV. Materials and Methods: Antisolvent precipitation method is used to prepare NRSV under temperature control. The following methods were used in this study, i.e., in vitro assessment of CYP3A activity in liver and intestinal microsomes and in vitro noneverted sac method. To confirm the in vitro findings, an in vivo pharmacokinetic study was also performed. Results: The results indicate that RSV significantly (P < 0.05) inhibited the CYP3A activity in intestinal and liver microsomes. In noneverted sac study, the intestinal transport and Papp of BRO were more significant (P < 0.05) in NRSV as compared to RSV group. Further, in vivo study revealed that the increased levels of Cmax and AUC were comparatively higher in NRSV-pretreated group than RSV group. In addition, pretreatment with RSV and NRSV significantly (P < 0.05) decreased the mean appararant clearance (CL/F) of BRO. Conclusion: NRSV pretreatment significantly increased the intestinal absorption and bioavailability of BRO probably by the inhibition of CYP3A-mediated metabolism in rats. However, further studies are needed to confirm these interactions in humans.
Keywords: Bromocriptine, CYP3A, high-performance liquid chromatography, oral bioavailability, resveratrol nanoparticles.