Add time:09/09/2019         Source:sciencedirect.com

The androgenic and the progestational activity of norgestimate (NORG) and levonorgestrel (LNG) were compared in two animal studies. During a Hershberger test in immature castrated male rats and a pregnancy maintenance test in pregnant rats, NORG and LNG were administered subcutaneously at several doses, serum samples were collected from each animal during the treatment period and the concentration of LNG was measured in these samples. It could be shown in both studies that in those animals which were treated with NORG, LNG was a major metabolite present in the serum. The difference in the pharmacological response in LNG- and NORG-treated rats was equivalent to the difference in the exposure of the animals to either directly administered or metabolically derived LNG. This was true for the androgenic and the progestational activity of NORG. It is concluded that according to the present results, NORG can be described as a pro-drug of LNG and that the latter is probably mainly responsible for the pharmacological effects observed during treatment with NORG. It cannot be excluded, however, that NORG itself or other metabolites of this drug may also contribute to the pharmacodynamic response.

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