Stereoselective disposition of ibuprofen enantiomers in man.
Stereoselective disposition of ibuprofen enantiomers in man.
复制标题
布洛芬对映体在人体中的立体选择性处置。
DOI：
10.1111/j.1365-2125.2004.02288.x
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发表时间：
1985
影响因子：
3.4
通讯作者：
D. Champion
中科院分区：
文献类型：
--
作者：
E. Lee;K. Williams;R. Day;G. Graham;D. Champion
本研究检测了布洛芬对映体在四个健康男性受试者中分别给予外消旋布洛芬（800毫克）和每个对映体（400毫克）后的立体选择性分布。R（-）布洛芬平均有63 +/- 6%的剂量被立体特异性地转化为S（+）对映体。没有可测量的S（+）到R（-）的反转。单个对映体的动力学通过同时施用各自的光学对映体而改变。这种变化很可能反映了血浆蛋白结合位点对映体之间的相互作用。发现葡萄糖醛酸酯缀合物的形成立体选择性地有利于S（+）对映体。数据表明，如果不研究单个对映体的药代动力学，就不能充分解释布洛芬和其他α -甲基乙酸的药代动力学。
This study has examined the stereoselective disposition of the enantiomers of ibuprofen in four healthy male subjects following separate administration of racemic ibuprofen (800 mg) and of each enantiomer (400 mg). A mean of 63 +/- 6% of an administered dose of R(-) ibuprofen was stereospecifically inverted to the S(+) enantiomer. There were no measurable inversion of the S(+) to R(-) ibuprofen. The kinetics of the individual enantiomers were altered by concurrent administration of the respective optical antipode. It is likely that this change reflects an interaction between the enantiomers at plasma protein binding sites. It was found that formation of ester glucuronide conjugates stereoselectively favoured the S(+) enantiomer. The data have demonstrated that the pharmacokinetics of ibuprofen and other alpha-methylarylacetic acids cannot be interpreted adequately without studying the pharmacokinetics of the individual enantiomers.