Identification of novel metabolites of pioglitazone in rat and dog
2003; Taylor & Francis; Volume: 33; Issue: 5 Linguagem: Inglês
10.1080/0049825031000085951
ISSN1366-5928
AutoresZ. Shen, James R. Reed, Mellissa Creighton, D. Q. Liu, Yiling Tang, D. F. Hora, William P. Feeney, Jason W. Szewczyk, Ray Bakhtiar, Ronald B. Franklin, Stella Vincent,
Tópico(s)Drug Transport and Resistance Mechanisms
Resumo1. Four new metabolites of pioglitazone were identified by liquid chromatography-mass spectrometry (LC-MS/MS) as being formed by hydroxylation (M-VII and M-VIII), opening of the thiazolidinedione ring (M-X) and by desaturation of the terminal ethyl side chain or tether ethoxy moiety (M-IX), respectively. The structure of one of the hydroxylated metabolites (M-VII) was confirmed by chemical modification using the Jones reaction. 2. Oxidative cleavage of the thiazolidinedione ring is a novel pathway not previously reported for pioglitazone. 3. The hydroxylated M-VII was detected in incubations with rat, dog and human liver and kidney microsomes, and in plasma from rats and dogs dosed orally with [3 H]pioglitazone. 4. The carboxylic acid derivative of M-VII (M-V) and its taurine conjugate were the major radioactive components in dog bile.
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