[Metabolism and pharmacokinetics of acemetacin in man (author's transl)].
Metabolism and pharmacokinetics of [1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetoxy]-acetic acid (acemetacin, TV 1322, Rantudil) in comparison to equimolar doses of indometacin was investigated in human volunteers after a single oral application and in rheumatic patients after multiple application. After multiple application (t.i.d. for 10 days) of equimolar doses of acemetacin and indometacin, mean blood level curves. The bioavailability of acemetacin derived from these data, corresponds to that of indometacin, i.e., approx. 100%, whereas after a single dose bioavailability of acemetcin is found to be smaller (66% from blood level, 64% from urine). This difference between single and multiple application is explained by slow filling-up of compartments. Degradation of acemetacin occurs by esterolytic cleavage to indometacin, by O-demethylation and N-desacylation and by partial conjugation of all these compounds to glucuronic acid. Blood level ratios of acemetacin and indometacin are equal after single and after multiple application of acemetacin. Therefore, degradation of acemetacin is not induced after multiple application. After a steady-state has been reached half-life of elimination is 4.5 +/- 2.8 h, which is longer than for indometacin (2.2 +/- 0.5 h). Interindividual differences are in the same range as described for indometacin.
D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D001682:Biological Availability; D001711:Biotransformation; D005260:Female; D006801:Humans; D007210:Indoleacetic Acids / Q000378:metabolism*; D007213:Indomethacin / Q000378:metabolism / Q000031:analogs & derivatives; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008297:Male; D013582:Synovial Fluid / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D007210:Indoleacetic Acids; C026784:acemetacin; D007213:Indomethacin
Metabolismus und Pharmakokinetik von Acemetacin beim Menschen.