title: The effect of hyperglycemia on the pharmacokinetics of valproic acid studied by high-performance liquid chromatography with electrochemical detection.
abstract: The effects of hyperglycemia on the pharmacokinetics of valproic acid (VPA) were examined by time-concentration profiles of plasma VPA accompanied with blood glucose (BG) changing. In addition, time-concentration profiles of plasma free fatty acids (FFAs) were also obtained to examine the interaction between VPA and FFAs in vivo. For the experiments in vivo, normal rats, given multiple doses of maltose orally, and diabetic rats, which were made to maintain hyperglycemia, were used. Plasma VPA and FFA were determined by high-performance liquid chromatography with electrochemical detection (HPLC-ECD) systems based on the reduction of quinone for the selective determination of acids, respectively. BG was determined by pocket-size glucose meter. The maximum plasma concentrations (Cmax) of VPA in normal rats given multiple doses of maltose orally and in diabetic rats were remarkably decreased in comparison with those in the control rats. From the present study, it was shown that the metabolism of plasma VPA is accelerated under hyperglycemia. Moreover, we also found that VPA was preferentially metabolized in comparison with the plasma FFA in vivo.
authors.affiliation: Department of Analytical Chemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. Electronic address: kotani@toyaku.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Kotani
authors.affiliation: Department of Analytical Chemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan; Division of Pharmacy, Tama Hospital, 2082 Nakano-cho, Hachioji, Tokyo 192-0015, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kotani
authors.affiliation: Department of Analytical Chemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Nana
authors.initials: N
authors.lastname: Ishii
authors.affiliation: Department of Analytical Chemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hakamata
authors.affiliation: Department of Analytical Chemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Kusu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental; D004347:Drug Interactions; D055664:Electrochemical Techniques; D005230:Fatty Acids, Nonesterified / Q000032:analysis / Q000097:blood; D006943:Hyperglycemia / Q000378:metabolism*; D057230:Limit of Detection; D008297:Male; D008320:Maltose / Q000008:administration & dosage; D051381:Rats; D015203:Reproducibility of Results; D013997:Time Factors; D014635:Valproic Acid / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D014635:Valproic Acid; D008320:Maltose
keywords: Free fatty acid; HPLC; Hyperglycemia; Pharmacokinetic parameter; Valproic acid