Effects of atorvastatin on pharmacokinetics of amlodipine in rats and its potential mechanism

Abstract

1. Atorvastatin combined with amlodipine (ALDP) can efficiently treat the hypertension with coronary heart disease. However, the drug-drug interaction between atorvastatin and ALDP are still unknown.

2. This study investigates the effects of atorvastatin on the pharmacokinetics of ALDP in rats and clarifies its main mechanism.

3. The pharmacokinetic profiles of oral administration of ALDP (1 mg/kg) in Sprague-Dawley rats, with or without pretreatment of atorvastatin (1.5 mg/kg/d for 7 d) were investigated. The effects of atorvastatin on the metabolism of ALDP were also investigated using rat liver microsomes.

4. The results showed that atorvastatin could significantly increase the peak plasma concentration (from 18.28 ± 2.65 to 24.13 ± 1.96 ng/mL) and decrease the oral clearance (from 4.57 ± 1.15 to 1.79 ± 0.28 L/h/kg) of ALDP. In the rat liver microsome systems, the intrinsic clearance rate of ALDP was decreased by the pretreatment with atorvastatin (39.26 ± 2.1 vs. 33.24 ± 3.3 μL/min/mg protein).

5. Those results indicated that atorvastatin could significantly affect the pharmacokinetic of ALDP, via inhibiting the metabolism of ALDP in rats.

Keywords:

• Atorvastatin
• amlodipine
• pharmacokinetics
• drug-drug interaction

Disclosure statement

The authors have reported that there is no conflict of interest.