Bioequivalence comparing an amlodipine/atorvastatin combination tablets to coadministration of amlodipine and atorvastatin tablets in healthy Chinese male subjects

Objective To evaluate the bioequivalence of one combination tablets(amlodipine 5 mg/atorvastatin 40 mg) and coadministration of one 5 mg amlodipine tablets and one 40 mg atorvastatin tablets.Methods A single oral dose(test and reference formulations) was given to 66 healthy male Chinese subjects according to an open randomized crossover design.Compounds were analyzed by GC-ECD and HPLC-MS/MS,respectively.WinNonlin and SAS software were used to calculate the pharmacokinetic parameters and evaluate the bioequivalence.Results Following administration of combination formulation(test) and coadministration formulation(reference),for amlodipine,tmax(median) was 6.0 and 6.0 h,t1/2 was(39.2±7.6) and(39.7±9.9) h,Cmax was(3.0±0.9) and(3.0±0.5) ng·mL-1,AUC0-∞ was(145.3±42.1) and(149.8 ± 43.6) ng·h·mL-1,respectively;for atorvastatin,tmax was 1.0 and 0.5 h,t1/2 was(6.7±1.8) and(6.9±1.8) h,Cmax was(18.8±9.8) and(20.2±11.7) ng·mL-1,AUC0-∞ was(101.7± 35.2) and(97.8±39.2) ng·h·mL-1,respectively.The estimated 90% CIs for the ratio of AUC0-t,AUC0-∞ and Cmax(test/reference) were 93.3%-100.1%,93.8%-100.6% and 95.8%-103.4% for amlodipine;99.2%-111.0%,99.6%-110.6% and 81.8%-107.2% for atorvastatin.Conclusion The combination formulation was bioequivalent to coadministration formulation.