Mayer J M
Ecole de Pharmacie, Université de Lausanne, Switzerland.
Acta Pharm Nord. 1990;2(3):197-216.
2-Arylpropionic acids (profens) are a major group of non-steroidal anti-inflammatory drugs. These compounds exist in two enantiomeric forms due to the presence of an asymmetric carbon atom alpha to the carbonyl function. In vitro tests have shown that the anti-prostaglandin synthetase activity of profens resides almost exclusively in the (+)-(S)-enantiomers, yet all profens except naproxen are marketed as racemates. The profens exhibit enantioselective pharmacokinetics, the most intriguing aspect of which is their unidirectional chiral inversion from the (-)-(R)- to the (+)-(S)-enantiomer. Since the transformation goes from the inactive to the pharmacologically active form, the (R)-enantiomer can be considered as a prodrug of its (S)-antipode. The available evidence suggests that this reaction proceeds via the formation of the acyl-CoA thioester of the 2-arylpropionates. Hutt and Caldwell have reviewed the literature describing this unusual metabolic process. The purpose of this paper is to present more recent findings from in vivo and in vitro studies and to summarize actual knowledge concerning the mechanism of the metabolic chiral inversion of profens.
2-芳基丙酸（丙酸类药物）是一大类非甾体抗炎药。由于羰基官能团的α位存在一个不对称碳原子，这些化合物以两种对映体形式存在。体外试验表明，丙酸类药物的抗前列腺素合成酶活性几乎完全存在于（+）-（S）-对映体中，但除萘普生外，所有丙酸类药物均以外消旋体形式上市。丙酸类药物表现出对映体选择性药代动力学，其中最引人关注的方面是它们从（-）-（R）-对映体单向手性转化为（+）-（S）-对映体。由于这种转化是从无活性形式转变为药理活性形式，（R）-对映体可被视为其（S）-对映体的前药。现有证据表明，该反应通过形成2-芳基丙酸酯的酰基辅酶A硫酯来进行。赫特和考德威尔已对描述这一异常代谢过程的文献进行了综述。本文的目的是介绍体内和体外研究的最新发现，并总结有关丙酸类药物代谢手性转化机制的实际知识。
