[Comparative metabolic studies on [14C]-labelled acemetacin and indometacin in rats (author's transl)].
1. [14C]-Indometacin and [14C]-Acemetacin are synthesized starting from carboxyl-[14C]-levulinic acid. 2. Renal, biliary and fecal elimination of both compounds occurs mainly within 24 h after intravenous or intraduodenal application to rats and after degradation to N-des-p-chlorobenzoyl- and O-des-methyl compounds and various conjugations. Main metabolite in urine and feces after both compounds is O-desmethyl-indometacin. A high percentage of unchanged indometacin besides small amounts of des-p-chlorobenzoylindometacin (DBI) and des-p-chlorobenzoyl-O-desmethylindometacin (DBMI) are found in bile. Both metabolites exist also in urine, bile and feces following administration of acemetacin. 3. After application of [1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetoxy]-acetic acid (acemetacin, TV 1322, Rantudil) free acemetacin is found to be 2.4% in urine, 7% in the bile and 3.5% in feces. In urine and bile additional amounts are present as conjugates. 4. Conjugation to sulfuric acid was found besides glucuronidation, i.e., O-desmethylindometacinsulfate (urine, bile) and des-p-chlorobenzoyl-O-desmethylindometacinsulfate (bile). indometacin glycine, a new conjugate, is formed after application of either acemetacin or indometacin. The renal proportion of this metabolite is three times higher after acemetacin than after indometacin, this can explain the better tolerance of acemetacin in comparison to indometacin. 5. metabolism of acemetacin and indometacin in the rat, as manifested by excretion into urine, bile and feces, is comparable on a qualitative basis if excretion of free acemetacin is neglected; there exist, however, quantitative differences.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D002250:Carbon Radioisotopes; D005243:Feces / Q000032:analysis; D007210:Indoleacetic Acids / Q000378:metabolism*; D007213:Indomethacin / Q000378:metabolism* / Q000031:analogs & derivatives; D007553:Isotope Labeling; D051381:Rats
D000893:Anti-Inflammatory Agents; D002250:Carbon Radioisotopes; D007210:Indoleacetic Acids; C026784:acemetacin; D007213:Indomethacin
Vergleichende metabolische Studien von [14C]-markiertem Indometacin und Acemetacin bei Ratten.