Effect of Curcuminoids on Pharmacokinetics and Pharmacodynamics of Atorvastatin in Hyperlipidemia Rats and Its Potential Mechanism

Abstract

Curcuminoids (CURs), natural polyphenols, are often combined with atorvastatin to treat hyperlipidemia. In order to assess the safety of combination, the effect of CURs on Cytochrome P450 (CYP) 3A2 activity in rats was investigated. Additionally, the effect of CURs on pharmacokinetics and pharmacodynamics of atorvastatin in rats was evaluated. The effect of CURs on CYP3A2 activity was studied using the probe drug method (dapsone as a probe drug). Pharmacokinetic parameters of atorvastatin with or without CURs were calculated to evaluate herb-drug interactions (HDIs). The effect of CURs on pharmacodynamics of atorvastatin was investigated by blood lipid, oxidative stress, aminotransferases, inflammatory factors and liver histopathology. C_max, AUC, and t_1/2 of dapsone in CURs group significantly increased (p < 0.05). C_max, AUC, and t_1/2 of atorvastatin in combination group significantly increased both in normal and hyperlipidemia rats (p < 0.01). Pharmacodynamics indexes of all treatment groups were significantly improved. There was no significant difference between AC group and combination group except HDL-C, SOD and liver index. In conclusion, CURs combined with atorvastatin could not effectively enhance the lipid-lowering effect or alleviate liver damage. However, CURs could inhibit CYP3A2 activity in rats and increase plasma exposure of atorvastatin, which might increase the risk of HDIs. The findings provided new insight into the combination of CURs and atorvastatin in treating hyperlipidemia.