Pharmacokinetics of sustained-release capsule of 5-isosorbide mononitrate in 20 healthy Chinese young men

AIM: To compare the pharmacokinetics of domestic and imported sustained-rel ease capsule of 5-isosorbide mononitrate (5-IM). METHODS: A single and 5-d- repeated oral doses of 5-IM 50 mg were performed on 2 groups of 20 Chinese healthy subjects (10 subjects for each group) in a randomized crossover pro tocol. The 5-IM in plasma were measured by gas chromatography with electron -captured detector method. Data were analyzed automatically by using a CAPP program on a PC computer. RESULTS: Fitting the 5-IM concentration-time cur ves to one-compartment model or following trapezoidal rule, the parameters such as T-max, C-max, K-e, MRT, and AUC were calculated and there were no s ignificant differences between the two kinds of capsule. The major pharmaco kinetic parameters of domestic and imported 5-IM sustained-release capsule with a 5-d multiple dose were respectively: C-max (677 +/- 103) and (702 +/ - 76) mu g.L-1; T-max (5.1 +/- 2.0) and (5.6 +/- 1.3) h; MRT (11.5 +/- 0.5) and (11.4 +/- 0.7) h; AUC(0-infinity) (12 121 +/- 1346) and (12 352 +/- 98 8) mu g.h.L-l. The fraction of drug absorbed in vivo was correlated well wi th the percentage amount of drug released in vitro at corresponding time (P < 0.05), and the fluctuation indices on d 5 in multiple dose study were no t significantly different between the two formulations (P > 0.05). The rela tive bioavailability of the domestic capsule for single and multiple dose w ere 96% +/- 11% and 98% +/- 10%, respectively. CONCLUSION: Domestic 5-IM su stained-release capsule showed bioequivalence compared with the imported ca psule and provided the same nitrate-low interval in the latter part of the 24-h dosing interval.