Pharmacokinetics of Three Organic Nitrates in Chinese Healthy Male Volunteers

Jun Chen; Xin Guo Jiang; Lei Cai; Wei Lu; Ke Pan Gao; Zheng Qi Shi; Qi Zhiang Zhang
April 2004
Drug Research / Arzneimittel-Forschung (Editio Cantor Verlag fur;Apr2004, Vol. 54 Issue 4, p203
Academic Journal
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, AUC0-7infin;, Cmax, tmax, t½, Kelm and MRT were determined for the three formulations and found to be in good agreement with literature values. AUC0-t and AUC0-∞ of 5-ISMN tablet and intravenous infusion were 2694 ± 496 ng · ml&sup-1; h vs. 2548 ± 556 ng · ml&sup-1; · h and 3266 ± 624 ng · ml&sup-1; · h vs. 3178 &plsumn; 769 ng · ml&sup01; · 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.


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