Kuhnz W, Beier S
Research Laboratories, Schering Aktiengesellschaft, Berlin, Germany.
Contraception. 1994 Mar;49(3):275-89. doi: 10.1016/0010-7824(94)90045-0.
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.
在两项动物研究中比较了诺孕酯（NORG）和左炔诺孕酮（LNG）的雄激素活性和孕激素活性。在对未成熟去势雄性大鼠进行的赫什伯格试验以及对怀孕大鼠进行的妊娠维持试验中，以几种剂量皮下注射NORG和LNG，在治疗期间从每只动物采集血清样本，并测量这些样本中LNG的浓度。两项研究均表明，在接受NORG治疗的动物中，LNG是血清中存在的主要代谢产物。LNG治疗组和NORG治疗组大鼠的药理反应差异等同于动物对直接给药或代谢衍生的LNG暴露量的差异。NORG的雄激素活性和孕激素活性均是如此。根据目前的结果得出结论，NORG可被描述为LNG的前体药物，后者可能主要负责NORG治疗期间观察到的药理作用。然而，不能排除NORG本身或该药物的其他代谢产物也可能对药效学反应有贡献。
