Pharmacokinetics of progesterone and its metabolites allopregnanolone and pregnanolone after oral administration of low-dose progesterone
Pharmacokinetics of progesterone and its metabolites allopregnanolone and pregnanolone after oral administration of low-dose progesterone
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DOI：
10.1016/j.maturitas.2005.11.005
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发表时间：
2006-06-20
期刊：
影响因子：
4.9
通讯作者：
Backstrom, T.
中科院分区：
文献类型：
--
作者：
Andreen, L.;Spigset, O.;Backstrom, T.
目的：为了研究孕酮，allopregnanolone和孕烯醇酮的药代动力学治疗后，与低口服剂量的progester.Methods：8名绝经后妇女被给予一个单一的口服剂量的20毫克的微粒化孕酮在第一天和20毫克，每天两次，在第2-7天。收集用于分析孕酮、别孕烯醇酮和孕烯醇酮的血液样品，并计算药代动力学参数。结果：单剂量摄入后，孕酮、别孕烯醇酮和孕烯醇酮的血浆浓度-时间曲线下面积（AUC）从0至12 h分别比估计由内源性产生引起的相应AUC高127%、196%和119%。孕烷醇酮的最大血浆浓度（C-max）和AUC值显著低于孕酮和别孕烷醇酮。稳态时的谷浓度（C1）显著高于基线值，孕烷醇酮的C-SS显著低于别孕烷醇酮和孕酮。C-SS为allopregnanolone是在什么是正常的范围内看到在月经cycle.Conclusions：摄入低剂量的孕酮后，allopregnanolone的浓度在相同的范围内，孕酮。口服剂量为20毫克的孕酮，每天两次给绝经后妇女产生的别孕烯醇酮浓度与绝经前妇女生理上达到的浓度相当。低剂量口服孕酮可用作前体药物别孕烯醇酮时，目的是研究低剂量别孕烯醇酮对人体的影响。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
Objectives: To investigate the pharmacokinetics of progesterone, allopregnanolone and pregnanolone after treatment with a low oral dose of progesterone.Methods: Eight postmenopausal women were given a single oral dose of 20 mg of micronised progesterone on Day I and 20 mg twice daily on Days 2-7. Blood samples for the analysis of progesterone, allopregnanolone and pregnanolone were collected, and pharmacokinetic parameters were calculated.Results: After ingestion of a single dose, areas under the plasma concentration-time curve (AUC) from 0 to 12 h for progesterone, allopregnanolone and pregnanolone were 127%, 196% and 119% higher than the corresponding AUCs estimated to be caused by endogenous production. The maximum plasma concentration (C-max) and the AUC values were significantly lower for pregnanolone than for progesterone and allopregnanolone. The trough concentrations at steady state (C,,) were significantly higher than the baseline values, and C-SS, for pregnanolone was significantly lower than for allopregnanolone and progesterone. C-SS for allopregnanolone was in the range of what is normally seen in the menstrual cycle.Conclusions: After ingestion of a low-dose of progesterone, the concentrations of allopregnanolone were in the same range as those of progesterone. Oral doses of 20 mg of progesterone twice daily to postmenopausal women produced allopregnanolone concentrations comparable to those achieved physiologically in premenopausal women. Low-dose oral progesterone may be used as a prodrug to allopregnanolone when the aim is to investigate low-dose allopregnanolone effects in humans. (c) 2005 Elsevier Ireland Ltd. All rights reserved.