Heald A F, Dizio D P, Kirkland K M, Loftus P, Malbica J O
Drug Metab Dispos. 1986 Nov-Dec;14(6):631-6.
The urinary metabolites of tracazolate [4-n-butylamino-1-ethyl-6-methyl-1H-pyrazolo (3,4-b) pyridine-5-carboxylic acid ethyl ester], an anxiolytic agent, obtained from rats and dogs dosed with 14C-labeled tracazolate have been characterized. No unchanged tracazolate was detected. Fifteen metabolites were identified in dog urine, seven of which had not previously been found in rat blood and tissue. Eleven of these metabolites were also found in rat urine. The metabolites were formed by deesterification to the 5-carboxylic acid; N-deethylation of the pyrazole ring: oxidation at the gamma-position of the n-butylamino side chain; oxidation of the terminal carbon of this side chain; loss of the n-butylamino group; and hydroxylation of the 6-methyl group followed by condensation with the 5-carboxylic acid to form gamma-lactones. The major metabolites in dog urine were the desethyl-desbutyl-deesterified compound, the desbutyl-deesterified compound, and the desbutyl-desethyl-lactone. Loss of the butyl side chain and, also, lactone formation, appeared to occur to a lesser extent in the rat than in the dog.
已对从给予14C标记曲卡唑酯的大鼠和犬体内获得的抗焦虑药曲卡唑酯[4-正丁氨基-1-乙基-6-甲基-1H-吡唑并(3,4-b)吡啶-5-羧酸乙酯]的尿液代谢产物进行了表征。未检测到未变化的曲卡唑酯。在犬尿液中鉴定出15种代谢产物，其中7种以前在大鼠血液和组织中未发现。这些代谢产物中有11种也在大鼠尿液中发现。代谢产物是通过酯水解为5-羧酸、吡唑环的N-去乙基化、正丁氨基侧链γ位的氧化、该侧链末端碳的氧化、正丁氨基的丢失以及6-甲基的羟基化随后与5-羧酸缩合形成γ-内酯而形成的。犬尿液中的主要代谢产物是去乙基-去丁基-去酯化化合物、去丁基-去酯化化合物和去丁基-去乙基内酯。大鼠体内丁基侧链的丢失以及内酯的形成似乎比犬体内的程度要小。
