Pharmacokinetics of three organic nitrates in Chinese healthy male volunteers.
Eighteen Chinese male subjects completed a single-blind, randomized, three-treatment, three-period, cross-over study. In each treatment phase, subjects received a single dose of 20 mg isosorbide dinitrate (CAS 87-33-2, ISDN) intravenous infusion, 20 mg isosorbide 5-mononitrate (CAS 16051-77-7, 5-ISMN) tablet or 20 mg isosorbide 5-mononitrate intravenous infusion. Each consecutive dosing was separated by a washout period of 7 days. Following each dosing, venous blood samples were collected over a period of 16 h. Plasma concentrations of ISDN and its two active metabolites isosorbide 2-mononitrate (2-ISMN), 5-ISMN had been measured by a validated gas chromatographic method. Various pharmacokinetic parameters including AUC0-t, AUC0-infinity, Cmax, tmax, t1/2, Kelm and MRT were determined for the three formulations and found to be in good agreement with literature values. AUC0-t and AUC0-infinity of 5-ISMN tablet and intravenous infusion were 2694 +/- 496 ng x ml(-1) x h vs. 2548 +/- 556 ng x ml(-1) x h and 3266 +/- 624 ng x ml(-1) x h vs. 3178 +/- 769 ng x ml(-1) x h, respectively, and the relative bioavailability of 5-ISMN tablet was 105 +/- 20%. As compared with 5-ISMN intravenous infusion, ISDN can rapidly reach the plateau concentration and metabolize to its active metabolites 5-ISMN and 2-ISMN, which both have vasodilator effect. The results of this study suggest that as evaluated from the pharmacokinetic profiles of the three formulations, 5-ISMN tablet and ISDN intravenous infusion are ideal vasodilators and anti-angina drugs especially in acute conditions due to their rapid onset and long duration of action.
Chen
Jun
J
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, The People's Republic of China.
Jiang
Xin Guo
XG
Cai
Lei
L
Lu
Wei
W
Gao
Ke Pan
KP
Shi
Zheng Qi
ZQ
Zhang
Qi Zhiang
QZ
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002849:Chromatography, Gas; D018592:Cross-Over Studies; D004562:Electrocardiography / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D009566:Nitrates / Q000493:pharmacokinetics*; D014665:Vasodilator Agents / Q000493:pharmacokinetics
D009566:Nitrates; D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate