Nakashima E, Rigod J F, Lin E T, Benet L Z
Department of Pharmacy, University of California, San Francisco 94143-0446.
Clin Pharmacol Ther. 1990 May;47(5):592-8. doi: 10.1038/clpt.1990.80.
The pharmacokinetics of nitroglycerin and the formation of its dinitrate metabolites (1,2-glyceryl dinitrate and 1,3-glyceryl dinitrate) were determined in six healthy volunteers after administration of six oral solution doses ranging from 0.4 mg to 13 mg. ANOVA analysis indicated significant differences between subjects for all Cmax/dose and AUC/dose measurements. No significant difference between doses were noted for these parameters except for AUC/dose for 1,3-glyceryl dinitrate. The ratio of metabolites (1,2-metabolite/1,3-metabolite) for the 0.4 mg dose was significantly different from the ratios for the doses of 1.6 mg or higher. Measurements of the combined residence time parameter suggest nonlinearity in nitroglycerin absorption and metabolism processes of AUMC/AUC between the 0.4 and the 13 mg doses. Consistent results were observed in the AUC ratios of metabolites for 0.4 mg doses of nitroglycerin between oral and sublingual administrations, suggesting that the increased metabolite ratio noted for sublingual nitroglycerin may reflect differences in dose, rather than differences in route of administration.
在六名健康志愿者服用0.4毫克至13毫克六种口服溶液剂量后，测定了硝酸甘油的药代动力学及其二硝酸盐代谢产物（1,2 - 甘油二硝酸盐和1,3 - 甘油二硝酸盐）的形成。方差分析表明，所有Cmax/剂量和AUC/剂量测量在受试者之间存在显著差异。除1,3 - 甘油二硝酸盐的AUC/剂量外，这些参数在剂量之间未观察到显著差异。0.4毫克剂量的代谢产物比率（1,2 - 代谢产物/1,3 - 代谢产物）与1.6毫克或更高剂量的比率显著不同。对组合停留时间参数的测量表明，0.4毫克和13毫克剂量之间硝酸甘油的吸收和代谢过程中AUMC/AUC存在非线性。在口服和舌下给药的0.4毫克剂量硝酸甘油的代谢产物AUC比率中观察到一致的结果，这表明舌下硝酸甘油注意到的代谢产物比率增加可能反映剂量差异，而非给药途径差异。
