The effect of esterases on 17alpha-hydroxyprogesterone caproate.
The effect of esterases on 17alpha-hydroxyprogesterone caproate.
复制标题
酯酶对 17α-羟基孕酮己酸酯的影响。
DOI：
10.1016/j.ajog.2007.07.038
复制
发表时间：
2008
影响因子：
9.8
通讯作者：
Nanovskaya,TatianaN
中科院分区：
文献类型：
--
作者：
Yan,Ru;Fokina,Valentina;Hankins,GaryDV;Ahmed,MahmoudS;Nanovskaya,TatianaN
目的研究17α-羟孕酮己酸酯在体外是否水解为17α-羟孕酮和己酸酯。研究设计研究了人血浆、肝脏和胎盘S9组分以及重组酯酶对双重放射性标记的17α-羟基-[3 H]孕酮[14 C]己酸酯的体外水解。采用配备在线放射性检测器的HPLC测定[3 H]-17α-羟孕酮和[14 C]-己酸的形成。羧酸酯酶和丁酰胆碱酯酶在人源性制剂中的存在和活性分别通过其原型底物乙酸对硝基苯酯、丁酸对硝基苯酯和丁酰硫代胆碱的水解来证实。结果上述人源性制剂均能水解乙酸对硝基苯酯、丁酸对硝基苯酯和丁酰硫代胆碱。然而，在相同的实验条件下，将17α-羟孕酮己酸酯与人源性制剂一起孵育时，未检测到[3 H]-17α-羟孕酮和[14 C]-己酸酯。结论17α-羟基孕酮己酸酯在体外不被人血浆、肝脏、早产儿和足月胎盘中的酯酶水解。
Objectives The aim of this investigation is to determine whether 17α-hydroxyprogesterone caproate is hydrolyzed, in vitro, to 17α-hydroxyprogesterone and caproate. Study design The in vitro hydrolysis of dual radioactively labeled 17α-hydroxy-[3H] progesterone [14C] caproate by human plasma, hepatic and placental S9 fractions as well as recombinant esterases was investigated. The formation of [3H]-17α-hydroxyprogesterone and [14C]-caproate were determined using HPLC equipped with an online radioactivity detector. The presence and activity of carboxylesterase and butyrylcholinesterase in the human derived preparations was confirmed by the hydrolysis of their prototypic substrates p-nitrophenyl acetate, p-nitrophenyl butyrate and butyrylthiocholine, respectively. Results The aforementioned human derived preparations hydrolyzed p-nitrophenyl acetate, p-nitrophenyl butyrate and butyrylthiocholine. However, when 17α-hydroxyprogesterone caproate was incubated with the human derived preparations under identical experimental conditions neither [3H]-17α-hydroxyprogesterone nor [14C]-caproate was detected. Conclusion 17α-Hydroxyprogesterone caproate is not hydrolyzed in vitro by the esterase enzymes present in human plasma, liver, preterm or term placenta.