Andréen L, Spigset O, Andersson A, Nyberg S, Bäckström T
Umeå Neurosteroid Research Center, Department of Clinical Science, Obstetrics and Gynecology, Norrlands University Hospital, SE-901 85 Umeå, Sweden.
Maturitas. 2006 Jun 20;54(3):238-44. doi: 10.1016/j.maturitas.2005.11.005. Epub 2006 Jan 6.
To investigate the pharmacokinetics of progesterone, allopregnanolone and pregnanolone after treatment with a low oral dose of progesterone.
Eight postmenopausal women were given a single oral dose of 20 mg of micronised progesterone on Day 1 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.
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 (Cmax) and the AUC values were significantly lower for pregnanolone than for progesterone and allopregnanolone. The trough concentrations at steady state (Css) were significantly higher than the baseline values, and Css for pregnanolone was significantly lower than for allopregnanolone and progesterone. Css for allopregnanolone was in the range of what is normally seen in the menstrual cycle.
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.
研究低口服剂量孕酮治疗后孕酮、别孕烯醇酮和孕烷醇酮的药代动力学。
8名绝经后女性在第1天单次口服20mg微粉化孕酮，在第2 - 7天每天口服2次，每次20mg。采集血样分析孕酮、别孕烯醇酮和孕烷醇酮，并计算药代动力学参数。
单次给药后，孕酮、别孕烯醇酮和孕烷醇酮在0至12小时的血浆浓度 - 时间曲线下面积（AUC）比内源性产生估计的相应AUC分别高127%、196%和119%。孕烷醇酮的最大血浆浓度（Cmax）和AUC值显著低于孕酮和别孕烯醇酮。稳态时的谷浓度（Css）显著高于基线值，孕烷醇酮的Css显著低于别孕烯醇酮和孕酮。别孕烯醇酮的Css处于月经周期中常见的范围内。
摄入低剂量孕酮后，别孕烯醇酮的浓度与孕酮浓度处于同一范围。绝经后女性每天口服2次20mg孕酮产生的别孕烯醇酮浓度与绝经前女性生理状态下达到的浓度相当。当旨在研究低剂量别孕烯醇酮对人体的影响时，低剂量口服孕酮可用作别孕烯醇酮的前体药物。
