title: Different serum concentrations of steady-state valproic acid in two sustained-release formulations.
abstract: Recently a new sustained-release formulation of valproic acid has been developed in Japan. The sustained-release mechanism of the new formulation was different from the conventional formulation. The aim of the present study was to compare the pharmacokinetic characteristics of valproic acid in two sustained-release formulations. Different sustained-release formulations of valproic acid (Depakene R and Selenica R) were administered in a randomized cross-over fashion in repeated doses in 24 psychiatric patients. After > or = 4 weeks administration of valproic acid once daily, blood samples were taken just before (0 h) and 8, 12, 24 h after the morning dose. Blood sampling was performed in the same manner in the same patients 4 weeks after switching from one to the other formulation of valproic acid. Serum concentrations of valproic acid at 0 h (50.7 +/- 19.4 vs 44.9 +/- 21.8 microg/mL, P < 0.05) and 24 h (52.3 +/- 19.54 vs 6.2 +/- 22.2 microg/mL, P < 0.05) were significantly higher during Selenica R than during Depakene R treatment, whereas the serum concentration of valproic acid at 8 h (49.7 +/- 19.2 vs 62.4 +/- 25.6 microg/mL, P < 0.01) was significantly lower during Selenica R treatment than during Depakene R treatment. Serum concentrations of valproic acid at 12 h were not different. The present study demonstrated that steady-state serum concentrations were different because of the different dissolution profiles. When a prescription for valproic acid is switched from one drug to the other, prescribers should be aware that the therapeutic drug monitoring data are not consistent.
authors.affiliation: Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, Japan. yasufuru@cc.hirosaki-u.ac.jp
authors.forename: Norio
authors.initials: N
authors.lastname: Yasui-Furukori
authors.forename: Manabu
authors.initials: M
authors.lastname: Saito
authors.forename: Taku
authors.initials: T
authors.lastname: Nakagami
authors.forename: Takenori
authors.initials: T
authors.lastname: Niioka
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sato
authors.forename: Akira
authors.initials: A
authors.lastname: Fujii
authors.forename: Sunao
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D012995:Solubility; D014635:Valproic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D014635:Valproic Acid