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Alteration in the plasma concentration of a DAAO inhibitor, 3-methylpyrazole-5-carboxylic acid, in the ketamine-treated rats and the influence on the pharmacokinetics of plasma d-tryptophan

A determination method for 3-methylpyrazole-5-carboxylic acid (MPC), an inhibitor of d-amino acid oxidase (DAAO), in rat plasma was developed by using high-performance liquid chromatography-mass spectrometry (LC-MS). The structural isomer of MPC, 3-methylpyrazole-4-carboxylic acid, was used as an in...

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Detalles Bibliográficos
Autores principales: HARUTA, Naomi, IIZUKA, Hideaki, ISHII, Kana, YOSHIHARA, Shunsuke, ICHIBA, Hideaki, FUKUSHIMA, Takeshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Japan Academy 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3311015/
https://www.ncbi.nlm.nih.gov/pubmed/22156410
http://dx.doi.org/10.2183/pjab.87.641
Descripción
Sumario:A determination method for 3-methylpyrazole-5-carboxylic acid (MPC), an inhibitor of d-amino acid oxidase (DAAO), in rat plasma was developed by using high-performance liquid chromatography-mass spectrometry (LC-MS). The structural isomer of MPC, 3-methylpyrazole-4-carboxylic acid, was used as an internal standard, and the intra- and inter-day accuracies and precisions were satisfactory for the determination of plasma MPC. Next, the LC-MS method was applied to determine the plasma MPC concentration in ketamine (Ket)-treated rats after intraperitoneal administration of MPC (5.0 or 50 mg·kg(−1)). The C(max) value of plasma MPC concentration in the Ket-treated rats was significantly higher than that in the control group when a high dose of MPC (50 mg·kg(−1)) was administered. In addition, it was found that plasma d-tryptophan (d-Trp) concentration in Ket-treated rats administered d-Trp was not significantly increased by MPC, suggesting that the DAAO-inhibitory effect of MPC is attenuated in Ket-treated rats.