title: 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.
abstract: 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.
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Chiba, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Haruta
authors.forename: Hideaki
authors.initials: H
authors.lastname: Iizuka
authors.forename: Kana
authors.initials: K
authors.lastname: Ishii
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yoshihara
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ichiba
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fukushima
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003605:D-Amino-Acid Oxidase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000097:blood*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D013058:Mass Spectrometry; D011720:Pyrazoles / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D014364:Tryptophan / Q000097:blood*
chemical_list: D004791:Enzyme Inhibitors; D011720:Pyrazoles; D007649:Ketamine; D014364:Tryptophan; D003605:D-Amino-Acid Oxidase; C005210:5-methylpyrazole-3-carboxylic acid