Pharmacokinetics and pharmacodynamic interaction of bergamottin with atorvastatin in rats

Abstract

1. The pharmacokinetics and pharmacodynamic of concomitant administration of atorvastatin with bergamottin were investigated perspectives to reveal the potential herb–drug interaction between these two drugs. 2. The hyperlipidaemia-induced Wistar rats received atorvastatin with or without bergamottin (2.5 mg/kg). The concentration of atorvastatin in the rats’ serum was determined using an established HPLC/MS/MS method. The pharmacokinetic parameters were calculated using DAS software. Lipid levels were determined. 3. Bergamottin increases the Cmax (from 48 ± 5 ng/mL to 89 ± 7 ng/mL), AUC0–∞ (from 176 ± 27 to 552 ± 131 h∗μg/L), and the elimination half-life of atorvastatin (t1/2) of atorvastatin. Co-administration of atorvastatin with bergamottin decreased total cholesterol (by 14%), low-density lipoproteins-cholesterol (by 20%), and triglyceride (by 12%), but increased thigh-density lipoprotein-cholesterol, when compared with atorvastatin alone. 4. Co-administration of bergamottin and atorvastatin alters both pharmacokinetics and pharmacodynamics of atorvastatin. This study provides pre-clinical information evidence that bergamottin could potentiate the therapeutic efficacy of atorvastatin or increase its accumulation and adverse effects.