The effects of phenytoin and carbamazepine on serum concentrations of mono-unsaturated metabolites of valproic acid

British Journal of Clinical Pharmacology
T KondoY Fukushima

Abstract

Serum concentrations of valproic acid (VPA) and its mono-unsaturated metabolites, 2-propyl-2-pentenoic acid (2-en), 2-propyl-3-pentenoic acid (3-en) and 2-propyl-4-pentenoic acid (4-en), were measured in 36 epileptic patients. The subjects were divided into three subgroups, i.e., receiving VPA alone (n = 20: VPA group), VPA with phenytoin (n = 9: VPA + DPH group), and VPA with carbamazepine (n = 7: VPA + CBZ group). In the VPA group, the correlations between the serum concentration of VPA and those of the metabolites were significantly positive (r = 0.693, P less than 0.01 for 2-en; r = 0.584, P less than 0.01 for 3-en; and r = 0.868, P less than 0.001 for 4-en). The concentration/dose ratio of VPA was significantly lower, and the 4-en/VPA ratio was significantly higher in the VPA + CBZ group than in the VPA group (P less than 0.05). However, DPH had less effect on the concentration/dose ratio of VPA and the 4-en/VPA ratio than CBZ. This may be due partly to the relatively smaller therapeutic dose of DPH. These results suggest a correlation between the serum concentration of VPA and that of 4-en, and an increased metabolic conversion of VPA to 4-en by coadministration of CBZ. High serum concentrations of VPA and concomitant use...Continue Reading

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Citations

Jun 19, 1992·Pharmaceutisch Weekblad. Scientific Edition·F Pisani
Sep 14, 2001·European Journal of Drug Metabolism and Pharmacokinetics·U KreherF Wien
Nov 11, 2010·Journal of Clinical Pharmacy and Therapeutics·I B BondarevaK I Bondareva
Oct 5, 2017·CNS Drugs·Bassel Abou-Khalil
Aug 26, 2009·Therapeutic Drug Monitoring·Goyo NagaiTsuyoshi Kondo
Jun 13, 2016·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Irma ConvertinoMarco Tuccori
Dec 14, 1999·Biopharmaceutics & Drug Disposition·B Blanco-SerranoA Domínguez-Gil

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