Effect of berberine on pharmacokinetics and pharmacodynamics of atorvastatin in hyperlipidemia rats

Abstract

1. Atorvastatin, an effective lipid-lowering drug, could reduce the risks of morbidity and mortality of cardiovascular diseases. Patients with cardiovascular diseases often use atorvastatin along with berberine. Atorvastatin is the substrate of CYP3A4 and P-gp. However, berberine is the inhibitor. The combination might lead to DDIs. The aim of this study was to assess the effect of berberine on pharmacokinetics and pharmacodynamics of atorvastatin in rats.

2. Plasma concentrations of atorvastatin with or without berberine were determined by HPLC. Pharmacokinetics parameters were calculated and used to evaluate pharmacokinetics interactions. The effect of berberine on pharmacodynamics of atorvastatin was investigated by detecting blood lipid, SOD, MDA, GSH-Px, AST, ALT, and liver histopathology.

3. C_max, t_max, and AUC_0-t of atorvastatin in combination group significantly increased both in normal and model rats (p < 0.01). The increase of t_1/2, AUC_0−t in model rats was more significant than that in normal rats (p < 0.05). Pharmacodynamics indexes in treatment groups were significantly improved, especially combination group (p < 0.05). Moreover, it could be found that there is a significant recovery in liver histopathology.

4. In conclusion, berberine could affect pharmacokinetics of atorvastatin, enhance lipid-lowering effect and improve liver injury in rats. More attention should be paid to plasma exposure in clinical to avoid adverse reactions.

Keywords:

• Atorvastatin
• berberine
• pharmacokinetics
• pharmacodynamics
• drug-drug interactions
• hyperlipidaemia

Disclosure statement

The authors report no declarations of interest.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and/or its supplementary materials.

Additional information

Funding

This research was supported by the Heilongjiang Provincial Administration of Traditional Chinese Medicine [ZHY2022-117] and the National Science Foundation of Heilongjiang Province [H2015044, LH2020H096, LH2021H102].