Pharmacokinetic parameters of an ester derivative of indomethacin

Abstract

The purpose of the study is to determine the pharmacokinetic parameters of a new ester derivative of indomethacin — codenamed indomenthyl — after its administration to rats. Indomenthyl was administered into stomach of rats as a solution in flaxseed oil: single administration at a dose of 12.5, 25 and 50 mg/kg, or multiple administration once a day at a dose of 50 mg/kg for 7 days. Blood plasma levels of indomenthyl and its active metabolite indomethacin were detected using a high-performance liquid chromatograph with the ultraviolet spectrophotometric detector.
It was shown that the value of the systemic exposure AUC of indomenthyl and indomethacin, released during its hydrolysis, increases linearly in the dose range of 12.5–50 mg/kg. On repeated (7-fold) administration indomenthyl and indomethacin do not cumulate in the organism. Thus, indomenthyl may be considered a safe retarded release form of indomethacin for the treatment of inflammatory diseases.