The effects of lacidipine on the steady/state plasma concentrations of simvastatin in healthy subjects

Aims Lacidipine, a long acting 2, 4-dihydropyridine calcium channel antagon ist is frequently administered with cholesterol lowering agents, particular ly in elderly populations. The effects of lacidipine on the pharmacokinetic s of simvastatin were investigated, since they share the CYP3A4 pathway for metabolism. Methods The study was an open, randomised, two-way crossover design, with a t least 7 days washout. Eighteen healthy subjects received simvastatin, 40 mg once daily, alone and together with lacidipine, 4 mg once daily, for 8 d ays. The pharmacokinetics of simvastatin were studied on the eighth day. An alysis was made of total simvastatin acid concentrations (naive simvastatin acid plus that derived from alkaline hydrolysis of the lactone). Results Lacidipine increased the maximum concentration of simvastatin (C-ma x) by approximately 70% (P=0.016) and the area under the plasma concentrati on-time curve AUC(0,24 h) by approximately 35% (P=0.001). The mean C-max an d AUC(0,24 h) of simvastatin (95% confidence interval) when given alone wer e 8.76 (6.72-11.41) ng ml(-1) and 60.36 (47.15-77.28) ng ml(-1) h. During t reatment with lacidipine they were, respectively, 14.89 (10.77-20.58) ng ml (-1) and 80.96 (64.62-101.44) ng ml(-1) h. No significant differences were observed in either time to peak concentration (t(max) was 1.0 h for simvast atin alone and 1.5 h for the combination) or in the half-life (t(1/2,z) was 8.5 h in both cases). The combination was safe and well tolerated. Conclusions The observed increased exposure to simvastatin 40 mg following coadministration of lacidipine is unlikely to be of clinical relevance.