Pharmacokinetics and bioequivalence of diltiazem hydrochloride sustained release tablets in healthy volunteers

Objective To determine the pharmacokinetics and bioequivalence of diltiazem hydrochloride test and reference preparation in healthy volunteers.Methods In the single dose study,120 mg of the test or the reference preparation was given to 18 healthy volunteers in a randomized two-period crossover study.In the multiple dose study,another 18 volunteers received diltiazem hydrochloride test or reference preparation for 7 days(60 mg,bid).Diltiazem concentration in the plasma was determined by HPLC-UV.Main pharmacokinetic parameters were calculated and compared by statistic analysis.Results The pharmacokinetic parameters of test and reference preparation obtained from the single dose study were as follows: AUC0~t was(901.71±270.84) and(926.82±277.02) ng·h·mL-1,AUC0~∞ was(974.58±292.88) and(995.85±291.13) ng·h·mL-1,Cmax was(97.66±26.36) and(101.78±33.54) ng·mL-1,tmax was(3.4±0.8) and(3.4±1.0)h,respectively.The relative bioavalability of the test preparation was(97.5±10.2)%.In the multiple dose study,the pharmacokinetic parameters were as follows: AUCss0~t was(803.42±205.68) and(783.22±181.62)ng·mL-1,AUCss was(566.67±128.14) and(549.59±112.58)ng·h·mL-1,Cssmax was(84.07±21.12) and(79.09±19.12)ng·mL-1,Cssmin was(27.34±5.81) and(27.21±5.02)ng·h·mL-1,Cav was(47.222±10.678) and(45.799±9.381)ng·mL-1,tmax was(3.0±0.3)and(3.1±0.4)h,DF was(1.19±0.26)and(1.12±0.24),respectively.The relative bioavalability of the test preparation was(102.6±12.5)%.Conclusion Analysis of variance and two one-sided t tests show that the test and reference preparation are bioequivalent.