[Study on major metabolites of 3H-1,2-dihydro-2-(4-methylphenylamino)-methyl-1-pyrrolizinone in rabbits].
The metabolites of a 750 mg oral dose of Z-47 [3H-1, 2-dihydro-2-(4-methylphenylamino) methyl-1-pyrrolizinone], a new anti-inflammatory and analgesic agent, in rabbit urine were separated and detected with high performance liquid chromatographic method. On basis of the chromatographic behavior of Z-47 metabolites and biotransformation pathways of drugs with partial structure of Z-47, the carboxylic derivative of Z-47 [4-(3H-1, 2-dihydro-1-pyrrolizinone-2-methylamino) benzoic acid] was proposed as a potential metabolite so that the compound was synthesized. The authentic substance was then compared with one of the metabolites by the chromatographic retention time and the ratio of their UV-absorbances at two wavelengths. The enzyme-hydrolyzed product of another metabolite was also analysed. It was consequently confirmed that the carboxylic derivative of Z-47 and its acyl beta-D-glucuronide are major metabolits of Z-47 in rabbits.
Zhong
D F
DF
Department of Pharmacy, Shenyang Pharmaceutical University.
Gu
J K
JK
Chen
R D
RD
Luo
X
X
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D008297:Male; D011758:Pyrroles / Q000378:metabolism*; D011817:Rabbits
C117067:3H-1,2-dihydro-2-(4-methylphenylamino)methy-1-pyrrolizinone; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011758:Pyrroles