The metabolism of zomepirac sodium. II. Isolation and identification of the urinary metabolites in rat, mouse, rhesus monkey, and man.
The metabolism of the oral analgesic agent, zomepirac sodium, sodium 5-(4-chlorobenzoyl)-1,4-dimethyl-1 H-pyrrole-2-acetate dihydrate, was studied in healthy male humans, rhesus monkeys, Wistar rats, and Swiss mice. The major urinary metabolites of zomepirac (Z) (80--95% of the dose) in these species were identified on the basis of a combination of chromatographic and spectroscopic data. Z was present as a major product in all species. Hydroxyzomepirac (HMZ) was a major component in rat and mouse, but a minor one in man, and it was absent in the monkey. 4-Chlorobenzoic acid (CBA) was identified as a major metabolite in rat (present as conjugates) and mouse and a minor one in monkey and man. Zomepirac glucuronide (ZG) was present as the major metabolite in man, monkey, and mouse, and present at trace levels in the rat. 4-Chlorohippuric acid, the glycine conjugate of CBA, was found in trace amounts only in the monkey. Thus, the metabolism of zomepirac in man and monkey is mainly characterized by glucuronide conjugation. The rat metabolizes zomepirac, mainly by oxidative pathways, to give HMZ and CBA. The mouse shows a balance of conjugation and oxidative pathways.
D000700:Analgesics / Q000652:urine*; D000818:Animals; D002723:Chlorobenzoates / Q000302:isolation & purification; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006626:Hippurates / Q000302:isolation & purification; D006801:Humans; D007700:Kinetics; D008253:Macaca mulatta; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D011758:Pyrroles / Q000652:urine*; D051381:Rats; D014046:Tolmetin / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000652:urine*
D000700:Analgesics; D002723:Chlorobenzoates; D006626:Hippurates; D011758:Pyrroles; C027367:hydroxyzomepirac; C027368:zomepirac glucuronide; C020549:zomepirac; C027366:4-chlorohippuric acid; D014046:Tolmetin