The pharmacokinetics of coumarin (C) upon i.v. and p.o. administration and its metabolites 7-hydroxy-coumarin (7-HC) and 7-hydroxy-coumarin glucuronide (7-HCG) have been studied. Six healthy volunteers were involved in this investigation. Four of the volunteers participated in a crossover study. Coumarin was administered i.v. and p.o. in dose sizes of 0.25 mg/kg and 0.857 mg/kg, respectively. Coumarin is rapidly absorbed p.o., however the availability to systemic circulation is less than 4%. The rest of the dose appears quantitatively as 7-HC and 7-HCG in systemic circulation suggesting an extensive firstpass effect. Coumarin and 7-HCG are best fitted to an open two-compartment model, whereas 7-HC is best fitted to an open one-compartment model. The biological half-life of both C (0.80 vs. 1.02 h) and 7-HCG (1.47 vs. 1.15 h) was not significantly different for the two routes of administration. The large total clearance of C again suggests a first-pass effect; while that of 7-HCG, which is nearly exclusively eliminated into urine, indicates active tubular secretion of the glucuronide.

中文翻译：

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香豆素在人体内静脉内和经口给药时的香豆素及其7-羟基代谢产物的药代动力学。

静脉和口服给药时，香豆素（C）及其代谢物7-羟基香豆素（7-HC）和7-羟基香豆素葡糖苷酸（7-HCG）的药代动力学已得到研究。六名健康志愿者参与了这项调查。其中四名志愿者参加了一项交叉研究。静脉内和口服给予香豆素，剂量分别为0.25mg / kg和0.857mg / kg。香豆素被迅速吸收，但是全身循环的利用率低于4％。其余剂量在全身循环中定量显示为7-HC和7-HCG，表明具有广泛的首过效应。香豆素和7-HCG最适合用于开放式两室模式，而7-HC最适合用于开放式一室模式。C（0.80 vs. 1.02 h）和7-HCG（1.47 vs. 1）的生物学半衰期 对于两种给药途径，15 h）没有显着差异。C的大清除率再次表明具有首过效应。而几乎完全排除在尿液中的7-HCG则表明葡萄糖醛酸的活性肾小管分泌。