Williams R L, Thakker K M, John V, Lin E T, Liang-Gee W, Benet L Z
Department of Medicine, University of California, San Francisco 94143.
Pharm Res. 1991 Jun;8(6):744-9. doi: 10.1023/a:1015802101272.
We recently compared plasma concentrations of nitroglycerin and its two dinitrate metabolites in 16 healthy male subjects after application of two controlled-release transdermal formulations of the drug. Analysis of the resulting plasma concentration-time curves indicated that the two formulations did not produce equivalent concentrations of parent drug or either of the dinitrate metabolites during the initial period of dosing. In addition, both formulations produced concentrations of the two dinitrate metabolites that exceeded the concentration of the parent drug by severalfold. Even if the pharmacologic effect of the dinitrate metabolites is low compared to that of nitroglycerin, these higher concentrations may contribute to the effect of nitroglycerin. Scrutiny of the ratio of 1,2-glyceryl dinitrate to 1,3-glyceryl dinitrate in the 16 subjects confirmed previous observations that preferential formation of the 1,2-glycerol dinitrate metabolite may occur depending on the route of administration. This ratio may thus be indicative of the bioavailability of nitroglycerin following transdermal application. Additional data suggesting racial differences in nitroglycerin absorption after transdermal application are presented.
我们最近比较了16名健康男性受试者在应用两种控释透皮制剂后血浆中硝酸甘油及其两种二硝酸盐代谢物的浓度。对所得血浆浓度-时间曲线的分析表明，在给药初期，这两种制剂产生的母体药物或任何一种二硝酸盐代谢物的浓度并不相等。此外，两种制剂产生的两种二硝酸盐代谢物的浓度比母体药物的浓度高出几倍。即使二硝酸盐代谢物的药理作用与硝酸甘油相比很低，但这些较高的浓度可能有助于硝酸甘油发挥作用。对16名受试者中1,2-二硝酸甘油与1,3-二硝酸甘油的比例进行仔细研究，证实了之前的观察结果，即根据给药途径，可能会优先形成1,2-二硝酸甘油代谢物。因此，该比例可能表明透皮应用后硝酸甘油的生物利用度。还提供了其他数据，表明透皮应用后硝酸甘油吸收存在种族差异。
