Goldzieher J W
Department of Obstetrics and Gynecology, Baylor College of Medicine.
Am J Obstet Gynecol. 1989 May;160(5 Pt 2):1260-4. doi: 10.1016/s0002-9378(89)80010-9.
Blood levels from a given oral dose of medication vary widely from patient to patient, even within a relatively homogeneous population, and from group to group across national borders. An important mechanism of inter-individual variation is the first pass through the enterohepatic circulation. When drugs such as ethinyl estradiol and norethindrone undergo this process, part of an orally administered dose is inactivated, which results in wide ranges of bioavailability. In connection with this process, these drugs are also susceptible to various drug-to-drug interactions. Levonorgestrel is not subject to first-pass extraction by the liver, which results in virtually 100% bioavailability. It is unclear whether interpopulation variations in blood levels result from ethnic, geographic, nutritional, or other phenomena. Hepatic mechanisms are qualitatively different as demonstrated by striking differences in urinary patterns of ethinyl estradiol conjugates and hydroxylations of ethinyl estradiol from country to country.
即使在相对同质的人群中，给予相同口服剂量药物后，不同患者的血药浓度也会有很大差异，而且不同国家人群之间也存在差异。个体间差异的一个重要机制是药物经肠肝循环的首过效应。当炔雌醇和炔诺酮等药物经历这一过程时，口服剂量的一部分会被灭活，这就导致了生物利用度的广泛差异。与此过程相关的是，这些药物也容易发生各种药物相互作用。左炔诺孕酮不会被肝脏首过清除，这使得其生物利用度几乎达到100%。尚不清楚血药浓度的人群间差异是由种族、地理、营养或其他因素引起的。不同国家炔雌醇结合物的尿排泄模式和炔雌醇羟化反应存在显著差异，这表明肝脏代谢机制在质上有所不同。
