Pharmacokinetics of sustained-release capsule of 5-isosorbide mononitrate in 20 healthy Chinese young men.
OBJECTIVE
To compare the pharmacokinetics of domestic and imported sustained-release 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 protocol. 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 curves to one-compartment model or following trapezoidal rule, the parameters such as Tmax, Cmax, Ke, MRT, and AUC were calculated and there were no significant differences between the two kinds of capsule. The major pharmacokinetic parameters of domestic and imported 5-IM sustained-release capsule with a 5-d multiple dose were respectively: Cmax (677 +/- 103) and (702 +/- 76) micrograms.L-1; Tmax (5.1 +/- 2.0) and (5.6 +/- 1.3) h; MRT (11.5 +/- 0.5) and (11.4 +/- 0.7) h; AUC0-infinity (12,121 +/- 1346) and (12,352 +/- 988) micrograms.h.L-1. The fraction of drug absorbed in vivo was correlated well with 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 not significantly different between the two formulations (P > 0.05). The relative bioavailability of the domestic capsule for single and multiple dose were 96% +/- 11% and 98% +/- 10%, respectively.


CONCLUSIONS
Domestic 5-IM sustained-release capsule showed bioequivalence compared with the imported capsule and provided the same nitrate-low interval in the latter part of the 24-h dosing interval.
Luo
W X
WX
Institute of Clinical Pharmacology, Nanjing Medical University, Nanjing 210029, China.
Zhang
Y D
YD
Shen
J P
JP
Ding
Y
Y
Huang
D K
DK
Luo
J P
JP
Qiu
J
J
Jiang
Z H
ZH
Peng
J H
JH
Sheng
L S
LS
D000328:Adult; D001682:Biological Availability; D002849:Chromatography, Gas; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D006801:Humans; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D008297:Male; D011897:Random Allocation; D014665:Vasodilator Agents / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate