Pharmacokinetics and pharmacodynamic interaction of bergamottin with atorvastatin in rats

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 C-max (from 48 +/- 5 ng/mL to 89 +/- 7 ng/mL), AUC(0-infinity) (from 176 +/- 27 to 552 +/- 131 h*mu g/L), and the elimination half-life of atorvastatin (t(1/2)) 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.