Pharmacokinetics of diltiazem hydrochloride delay-onset sustained-release pellet capsules in healthy volunteers

Objective To determine diltiazem in the human plasma by reversed-phase high-performance liquid chromatography(RP-HPLC),and to study the pharmacokinetics of diltiazem hydrochloride delay-onset sustained-release pellet capsules in healthy volunteers.Methods Three single oral doses(90,180 mg,and 270 mg) and a multiple oral dose(90 mg·d-1*6d) were given to 24 volunteers in an open randomized parallel design.Plasma concentrations of diltiazem were determined by RP-HPLC.Its pharmacokinetic parameters were calculated by DAS Ver 2.0.Results The main pharmacokinetic parameters of diltiazem hydrochloride delayed-onest sustained-release pellet capsules after a single oral 90,180,and 270 mg were as follows: tmax was(8.8±2.0),(10.5±1.4),and(11.0±1.1)h;Cmax was(67.43±32.74),(169.44±92.00),and(191.23±81.81)ng·mL-1;t1/2βwas(14.6±7.8),(16.9±6.3),and(16.0±6.1)h;AUC0~t was(1 018.1±524.3),(3 069.1±1 727.7),and(3 749.5±1 557.5)ng·h·mL-1;AUC0~∞ was(1 470.5±814.7),(4 556.2±3 128.3),and(5 042.9±1 861.7)ng·h·mL-1.The main pharmacokinetic parameters of diltiazem hydrochloride delayed-onset sustained-release pellet capsules after a multiple oral dose were as follows: tmax was(9.0±2.3)h;Cmax was(81.92±33.70)ng·mL-1;t1/2β was(14.3±7.7)h;AUC0~t was(1 365.9±569.5)ng·h·mL-1;AUC0~∞was(1 814.5±1 021.8)ng·h·mL-1;Cav was(46.66±16.36)ng·mL-1;and DF was(1.1±0.4).Conclusion Diltiazem hydrochloride delay-onset sustained-release pellet capsules had marked characteristics of delayed and controlled release.