Valproic acid has temporal variability in urinary clearance of metabolites

Reith, David M., Andrews, Jaymie and McLaughlin, Dan (2001) Valproic acid has temporal variability in urinary clearance of metabolites. Chronobiology International, 18 1: 123-129. doi:10.1081/CBI-100001176


Author Reith, David M.
Andrews, Jaymie
McLaughlin, Dan
Title Valproic acid has temporal variability in urinary clearance of metabolites
Journal name Chronobiology International   Check publisher's open access policy
ISSN 0742-0528
Publication date 2001-01-01
Sub-type Article (original research)
DOI 10.1081/CBI-100001176
Volume 18
Issue 1
Start page 123
End page 129
Total pages 7
Editor Ludger Rensing
Michael Smolensky
Place of publication New York, N.Y. U.S.A.
Publisher Marcel Dekker Inc
Language eng
Subject C1
320599 Pharmacology not elsewhere classified
730104 Nervous system and disorders
Abstract The reasons for the intra- and interindividual variability in the clearance of valproic acid (VPA) have not been completely characterized. The aim of this study was to examine day-night changes in the clearance of 3-oxo-valproate (3-oxo-VPA), 4-hydroxy-valproate (4-OH-VPA), and valproic acid glucuronides under steady state. Six diurnally active healthy male volunteers ingested 200 mg sodium valproate 12 hourly, at 0800 and 2000, for 28 days. On the last study day, two sequential 12-h urine samples were collected commencing at 2000 the evening before. Plasma samples were obtained at the end of each collection. Following alkaline hydrolysis, urine was analyzed for concentrations of VPA, 3-oxo-VPA, and 4-OH-VPA. A separate aliquot was assayed for creatinine (CR). The plasma concentrations of VPA, 3-oxo-VPA, 2-en-VPA, and CR were determined. The analysis of VPA and its metabolites was performed by CC-MS. There was an increase in plasma 3-oxo-VPA concentration at 0800, sampling as compared to 2000 sampling (p < .05). The urinary excretion of 3-oxo-VPA and VPA glucuronides were decreased between 2000 and 0800, compared to between 0800, and 2000, by 30% and 50% respectively (p < .05). These results indicate a nocturnal decrease in renal clearance of 3-oxo-VPA rather than a decrease in the beta -oxidation of VPA at night. These differences were not explained by differences between the sampling periods in CR excretion. These results indicate the importance of collecting samples of 24-h duration when studying metabolic profiles of VPA.
Keyword Biology
Physiology
Valproate
Clearance
Day-night
Metabolism
Renal
Sodium Valproate
Mice
Pharmacokinetics
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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Created: Wed, 15 Aug 2007, 01:42:13 EST