These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Pharmacokinetics of gestagens: some problems.
    Author: Fotherby K.
    Journal: Am J Obstet Gynecol; 1990 Jul; 163(1 Pt 2):323-8. PubMed ID: 2115297.
    Abstract:
    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. The results of previously published studies of the pharmacokinetics of levonorgestrel (LNG), a widely used gestagen, were tabulated, reviewed, and subjected to new analyses. The mean half-life of elimination, usually calculated using two-compartment open modeling, ranged from 8 to 18 hours. Such large variations in half-life of elimination have been noted in studies of other steroid contraceptives as well. Recalculation of half-life of elimination by simply plotting the 8- and 24-hour serum concentrations against time yielded values in general agreement with those obtained with the original investigators' pharmacokinetic values. The pharmacokinetics of gestagens are influenced not only by dose and formulation but also by high levels of intrasubject and intersubject variation. In most studies, sampling is not continued beyond 24 hours, and this may cause an underestimation of half-life, particularly for long-lived gestagens. Another common parameter, mean pharmacokinetic bioavailability of LNG (as calculated by the area under the curve method), ranged from 20 to 35 ng/ml/hour in patients given 150 mcg of LNG with 30 mcg of ethinyl estradiol. Bioavailability increased with higher doses. Since half of the LNG in serum is bound to sex hormone-binding globulin (SHBG), changes in the serum concentration of this protein may affect LNG pharmacokinetics. Estrogens induced SHBG. Some investigators have proposed that the higher LNG levels observed in serum when a gestagen is administered together with an estrogen is due to increased amounts of SHBG in serum. However, a number of studies have shown that estrogens administered with gestagens do not induce SHBG and may actually decrease its concentration. In general, studies of the pharmacokinetics of estrogens report a high degree of variation in common pharmacokinetic parameters, as well as a frequent lack of correlation with biologic response. This raises the question of whether these types of studies are providing useful information.
    [Abstract] [Full Text] [Related] [New Search]