Schubert W, Cullberg G, Hedner T
Department of Obstetrics and Gynaecology, University of Göteborg, East Hospital, Sweden.
Eur J Clin Pharmacol. 1993;44(6):563-8. doi: 10.1007/BF02440860.
A randomised, single-blind comparative study was carried out in 9 ovariectomized women to evaluate the kinetics of single doses of three different steroid combinations: 0.150 mg desogestrel + 2.0 mg micronized 17 beta-oestradiol, 0.150 mg desogestrel + 0.500 mg 17 beta-oestradiol cyclo-octyl acetate and 0.150 mg desogestrel + 1.0 mg 17 beta-oestradiol decanoate. Serum levels of 17 beta-oestradiol and oestrone were measured, as well as the excretion of 17 beta-oestradiol and its metabolites (oestrone and oestriol) in urine. In relation to the doses given, higher peak serum concentrations of 17 beta-oestradiol were obtained after the two fat soluble analogues, while the AUCs were similar to that after micronised 17 beta-oestradiol. However, there was more extensive conversion of the micronised 17 beta-oestradiol preparation into oestrone compared to 17 beta-oestradiol cyclo-octyl acetate and 17 beta-oestradiol decanoate. The oestrone/17 beta-oestradiol serum concentration ratio was approximately 2.6 before tablet intake and remained essentially unchanged after intake of 17 beta-oestradiol cyclo-octyl acetate and 17 beta-oestradiol decanoate. After micronized 17 beta-oestradiol however, there was a 2-3-fold increase in the ratio at Cmax and slower elimination of 17 beta-oestradiol from plasma, which may be due to the fact that high serum oestrone levels may serve as a reservoir, since both a metabolite and also a precursor of 17 beta-oestradiol. The urinary excretion of 17 beta-oestradiol, oestrone and oestriol was highest after oral administration of micronized 17 beta-oestradiol compared to 17 beta-oestradiol cyclo-octyl acetate and 17 beta-oestradiol decanoate.(ABSTRACT TRUNCATED AT 250 WORDS)
对9名卵巢切除的女性进行了一项随机、单盲对照研究，以评估三种不同甾体组合单剂量给药后的动力学情况：0.150毫克去氧孕烯 + 2.0毫克微粉化17β - 雌二醇、0.150毫克去氧孕烯 + 0.500毫克17β - 雌二醇环辛酯以及0.150毫克去氧孕烯 + 1.0毫克17β - 雌二醇癸酸酯。检测了血清中17β - 雌二醇和雌酮的水平，以及尿液中17β - 雌二醇及其代谢产物（雌酮和雌三醇）的排泄情况。就给药剂量而言，两种脂溶性类似物给药后血清中17β - 雌二醇的峰值浓度更高，而曲线下面积与微粉化17β - 雌二醇给药后相似。然而，与17β - 雌二醇环辛酯和17β - 雌二醇癸酸酯相比，微粉化17β - 雌二醇制剂转化为雌酮的程度更高。服用片剂前雌酮/17β - 雌二醇血清浓度比约为2.6，服用17β - 雌二醇环辛酯和17β - 雌二醇癸酸酯后基本保持不变。然而，服用微粉化17β - 雌二醇后，该比值在峰浓度时增加了2至3倍，且17β - 雌二醇从血浆中的消除速度减慢，这可能是因为高血清雌酮水平可作为一个储备库，因为它既是17β - 雌二醇的代谢产物也是其前体。与17β - 雌二醇环辛酯和17β - 雌二醇癸酸酯相比，口服微粉化17β - 雌二醇后，尿液中17β - 雌二醇、雌酮和雌三醇的排泄量最高。（摘要截选至250字）
