Dell H D, Jacobi H, Kamp R, Kolle J
Arzneimittelforschung. 1981;31(1):21-6.
Renal elimination of etofenamate was studied after oral (200--1200 mg/kg) and intravenous (75 mg/kg) application to dogs. Free flufenamic acid and total fenamates (except phenolic metabolites) were determined. In accordance with other N-arylanthranilic acid derivatives after etofenamate only small amounts are renally eliminated; these results are specific for dog and differ to other animal species. Renally eliminated amounts (up to 8%) are not dependent on dose, the i.v. results also being in the same range. Proportions of free flufenamic acid is small in comparison to total fenamates. Renal elimination occurs preferentially on the first day after application. Biliary elimination of etofenamate and its metabolites was investigated after intravenous as well as intragastric application. Intact etofenamate was found after i.v. and i.g. application, part of it being conjugated. Hydroxyderivatives of Etofenamate (eto) were identified: 5-OH-eto (i.v. and i.g.), 4'-OH-eto (i.v.) and the 5.4'-dihydroxy-eto (i.g.). A further eto-derivative found after i.v. application could not be characterized. Amounts of flufenamic acid (flu) and its hydroxyderivatives (esp. 5-OH-flu) were increased after hydrolytic degradation. These results show that metabolic degradation does not occur primarily be conversion to flufenamic acid; etofenamate itself is degraded by hydroxylation and/or conjugation and subsequent formation of the corresponding flufenamic derivatives.
对犬口服（200 - 1200毫克/千克）和静脉注射（75毫克/千克）依托芬那酯后，研究其经肾脏的排泄情况。测定了游离氟芬那酸和总芬那酸盐（酚类代谢物除外）。与其他N - 芳基邻氨基苯甲酸衍生物一样，依托芬那酯经肾脏排泄的量很少；这些结果是犬特有的，与其他动物物种不同。经肾脏排泄的量（高达8%）不依赖于剂量，静脉注射的结果也在相同范围内。与总芬那酸盐相比，游离氟芬那酸的比例较小。肾脏排泄主要发生在用药后的第一天。研究了依托芬那酯及其代谢物经静脉注射和胃内给药后的胆汁排泄情况。静脉注射和胃内给药后均发现了完整的依托芬那酯，部分已结合。鉴定出了依托芬那酯（eto）的羟基衍生物：5 - OH - eto（静脉注射和胃内给药）、4'- OH - eto（静脉注射）和5,4'- 二羟基 - eto（胃内给药）。静脉注射后发现的另一种依托芬那酯衍生物无法鉴定其特征。水解降解后，氟芬那酸（flu）及其羟基衍生物（尤其是5 - OH - flu）的量增加。这些结果表明，代谢降解主要不是通过转化为氟芬那酸发生的；依托芬那酯本身通过羟基化和/或结合以及随后形成相应的氟芬那酸衍生物而降解。
