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

作者：Haruta Naomi; Iizuka Hideaki; Ishii Kana; Yoshihara Shunsuke; Ichiba Hideaki; Fukushima Takeshi^*

来源：Proceedings of the Japan Academy Series B-Physical and Biological Sciences, 2011, 87(10): 641-648.

DOI：10.2183/pjab.87.641

• 3-methylpyrazole-5-carboxylic acid
• D-amino acid oxidase
• inhibitor
• rat
• ketamine
• D-tryptophan

A determination method for 3-methylpyrazole-5-carboxylic acid (M PC) an inhibitor of ID-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.

• 出版日期2011-12