[Studies on metabolism and elimination of etofenamate by dogs (author's transl)].

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.