Fotherby K
Royal Postgraduate Medical School, London, England.
Am J Obstet Gynecol. 1990 Jul;163(1 Pt 2):323-8. doi: 10.1016/0002-9378(90)90576-s.
Various approaches to studying the pharmacokinetics of gestagens and the factors that influence derivation of the parameters are described with levonorgestrel used as an example. Published studies of the pharmacokinetics of levonorgestrel are reviewed, and new information is presented regarding intra- and intersubject variation. Differences between various formulations of levonorgestrel are apparent when the formulations are compared in the same subjects. There is also a marked difference in the parameters when derived under single-dose or steady-state conditions. The role of sex hormone-binding globulin in the metabolism of levonorgestrel is questioned. Large intra- and inter-subject variations in the parameters exist, and a subject may show a large month-to-month variation when one levonorgestrel formulation is used and smaller variations when another formulation is used. This wide variability in the pharmacokinetic parameters, problems that arise in the derivation and interpretation of the parameters, the biologic significance of most of these parameters, and their lack of correlation with pharmacodynamic responses severely limit the usefulness of pharmacokinetic studies of the gestagens.
以左炔诺孕酮为例，描述了研究孕激素药代动力学的各种方法以及影响参数推导的因素。综述了已发表的左炔诺孕酮药代动力学研究，并给出了关于个体内和个体间变异的新信息。当在同一受试者中比较不同制剂时，左炔诺孕酮不同制剂之间的差异很明显。在单剂量或稳态条件下推导参数时，参数也存在显著差异。对性激素结合球蛋白在左炔诺孕酮代谢中的作用提出了质疑。参数存在较大的个体内和个体间变异，当使用一种左炔诺孕酮制剂时，受试者可能表现出较大的逐月变异，而使用另一种制剂时变异较小。药代动力学参数的这种广泛变异性、参数推导和解释中出现的问题、大多数这些参数的生物学意义以及它们与药效学反应缺乏相关性，严重限制了孕激素药代动力学研究的实用性。
