Non-concurrent dosing attenuates the pharmacokinetic interaction between amlodipine and simvastatin

Abstract

Objectives: To explore if non-concurrent amlodipine dosing results in less drug interaction, the pharmacokinetic profiles, safety and efficacy endpoints were assessed following repeated doses of simvastatin, co-administered concurrently or non-concurrently with amlodipine in patients with coexisting hypertension and hyperlipidemia. Methods: Seventeen patients randomly received daily doses of 20 mg simvastatin and 5 mg amlodipine for 6 weeks, either with both drugs at 7:00 PM (concurrent) or with simvastatin at 7:00 PM followed by amlodipine at 11:00 PM (non-concurrent). The maximum plasma concentration (C-max) and the area under the concentration-time curve up to the last quantifiable concentration (AUC(last)) were estimated at steady state. Lipid profiles and blood pressure values were also compared between the concurrent and non-concurrent groups. Results: The C-max and AUC(last) and of simvastatin acid in the non-concurrent amlodipine dosing group were 63.2% and 66.0%, respectively, of the values obtained in the concurrent group (1.2 +/- 1.0 vs. 1.9 +/- 0.9 ng/ml and 10.3 +/- 8.3 vs. 15.6 +/- 7.5 h ng/ml, respectively, mean standard deviation). Changes from baseline in lipid profile and blood pressure were comparable between the groups. Conclusions: Non-concurrent dosing may be a useful and safe therapeutic option for patients who require two or more drugs administered concomitantly, but who are likely to develop unwanted drug interactions.