RR,SS-苏式-甲基苯丙胺在体外被血液酯酶水解——种间差异及对映体选择性变异性

In vitro hydrolysis of RR,SS-threo-methylphenidate by blood esterases--differential and enantioselective interspecies variability.

作者信息

Srinivas N R, Hubbard J W, McKay G, Hawes E M, Midha K K

机构信息

College of Pharmacy, University of Saskatchewan, Saskatoon, Canada.

出版信息

Chirality. 1991;3(2):99-103. doi: 10.1002/chir.530030204.

DOI:10.1002/chir.530030204

PMID:1863524

Abstract

Enantioselective in vitro hydrolysis of methylphenidate (MPH) by the blood esterases of seven mammalian species is reported. The species included rats, rabbits, dogs, cattle, horses, monkeys, and humans. In vitro incubations up to 8 h were carried out in plasma, red blood cells, and whole blood of the various species. Enantioselective differences were evident among the different species on comparison of the data obtained from the three biological fluids. The esterases present in plasma appeared to show greater activity in the hydrolysis of MPH in all species where comparison with the other two biofluids was possible. Only in the case of humans did esterases present in plasma and red blood cells demonstrate opposite enantioselectivity in the hydrolysis of MPH. Thus after 8 h incubation, the RR-MPH/SS-MPH ratios in plasma and red blood cells were 0.31 and 1.16, respectively.

摘要

报道了七种哺乳动物血液酯酶对哌醋甲酯（MPH）的对映选择性体外水解情况。这些物种包括大鼠、兔子、狗、牛、马、猴子和人类。在不同物种的血浆、红细胞和全血中进行了长达8小时的体外孵育。从三种生物流体获得的数据比较表明，不同物种之间存在明显的对映选择性差异。在所有能够与其他两种生物流体进行比较的物种中，血浆中的酯酶在MPH水解中似乎表现出更高的活性。只有在人类的情况下，血浆和红细胞中的酯酶在MPH水解中表现出相反的对映选择性。因此，孵育8小时后，血浆和红细胞中RR-MPH/SS-MPH的比值分别为0.31和1.16。