Pharmacokinetics and toxicokinetics of D-serine in rats

Publication date: Available online 14 September 2018Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Hiroshi Hasegawa, Nami Masuda, Hiromi Natori, Yoshihiko Shinohara, Kimiyoshi IchidaAbstractIn the mammalian brain, D-serine acts as a co-agonist at the glycine-binding site on the N-methyl-D-aspartate receptor. Because plasma D-serine levels are significantly lower in patients with schizophrenia than in healthy subjects, D-serine has been proposed as a potential therapeutic agent for schizophrenia treatment. However, D-serine has a nephrotoxic effect in rats at high doses. The purpose of this study was to investigate the relationship between the plasma kinetics of D-serine and nephrotoxicity in rats. We administered D-serine intravenously (iv), orally (po), or intraperitoneally (ip) to male Wistar rats, and performed gas chromatography-mass spectrometry to measure the plasma concentrations of D- and L-serine. After iv administration (0.1 mmol/kg body weight (bw)), plasma D-serine declined multiexponentially with an elimination t1/2 of 108 ± 16 min, and the total clearance was 7.9 ± 0.9 ml/min/kg bw. The oral bioavailability of D-serine was estimated to be 94 ± 27%. To evaluate the dose–response relationship of D-serine-induced kidney injury and the plasma kinetics of D-serine, we injected D-serine into rats ip in doses ranging from 0.6 to 4.8 mmol/kg bw. Twenty-f...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research

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