Levonorgestrel. Clinical pharmacokinetics

Published values for the serum concentrations and pharmacokinetic parameters of levonorgestrel after administration of various doses of levonorgestrel alone or with ethinylestradiol are reviewed. Most data apply to oral administration of the gestagen, with the smaller amount of data for other modes of administration, e.g. subcutaneous, intravaginal and intra-uterine administration, also included. There is a large variability among the different studies for both serum concentration and pharmacokinetic parameters and not all of this is due to the large interindividual variability demonstrated in all of the studies. The factors responsible for the inter- and intraindividual variability have not been discovered. Sex hormone binding globulin (SHBG) plays an important role in levonorgestrel pharmacokinetics since: (i) levonorgestrel binds strongly to this protein; and (ii) serum SHBG levels are influenced by a large number of different factors including the administration of levonorgestrel and ethinylestradiol. However, not all of the anomalies in the metabolism of levonorgestrel can be ascribed to its interaction with SHBG.