Geisslinger G, Menzel-Soglowek S, Beck W S, Brune K
Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Germany.
Agents Actions Suppl. 1993;44:31-6.
The enantioselective pharmacokinetic behaviour of the flurbiprofen enantiomers was investigated following administration of optically pure R- or S-flurbiprofen to various species. Only negligible inversion (< 5%) of flurbiprofen occurred in the rat and in man. Consequently, pharmacodynamic experiments evaluating pain and inflammation as parameters have been carried out enantioselectively for both flurbiprofen enantiomers in the rat. R-flurbiprofen, which is not an inhibitor of prostaglandin synthesis in vitro, had only marginal anti-inflammatory effects as defined by the carrageenan edema of the rat paw in contrast to the S-enantiomer. In contrast, to S-flurbiprofen, R-flurbiprofen caused only marginal mucosal damage in the GI-tract. Both enantiomers, however, were of similar potency as antinociceptive drugs in the rat Randall-Selitto assay following the injection of interleukin-1 or baker's yeast. Using the pure enantiomers of flurbiprofen it appears possible to establish a more specific drug treatment: the R-enantiomer in occasional pain, the S-enantiomer in rheumatic disorders.
给不同物种分别施用光学纯的R-或S-氟比洛芬后，研究了氟比洛芬对映体的对映选择性药代动力学行为。在大鼠和人体内，仅发生了可忽略不计的氟比洛芬转化（<5%）。因此，已经在大鼠体内对两种氟比洛芬对映体进行了对映选择性的药效学实验，以疼痛和炎症作为参数。R-氟比洛芬在体外不是前列腺素合成的抑制剂，与S-对映体相比，根据大鼠爪部角叉菜胶水肿情况，其抗炎作用微弱。相反，与S-氟比洛芬相比，R-氟比洛芬在胃肠道仅引起轻微的黏膜损伤。然而，在注射白细胞介素-1或面包酵母后，两种对映体在大鼠Randall-Selitto试验中作为抗伤害感受药物的效力相似。使用氟比洛芬的纯对映体似乎有可能建立一种更具特异性的药物治疗方法：R-对映体用于偶尔疼痛，S-对映体用于风湿性疾病。
