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Chronopharmacokinetic Study of Valproic Acid in Man: Comparison of Oral and Rectal Administration
Author(s) -
Yoshiyama Yuji,
Nakano Shigeyuki,
Ogawa Nobuya
Publication year - 1989
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1989.tb03277.x
Subject(s) - morning , evening , pharmacokinetics , oral administration , medicine , rectal administration , valproic acid , circadian rhythm , dosing , pharmacology , anesthesia , epilepsy , physics , astronomy , psychiatry
Circadian stage‐dependent changes of valproic acid (VPA) kinetics was examined after rectal administration comparing after oral dosing. Eight healthy volunteers took a single oral or rectal dose of VPA 400 mg, in a form of sodium valproate, on two occasions, at 8:30 A.M. or 8:30 P.M. Subjects were synchronized with diurnal activity and nocturnal rest as their usual life under standardized meal conditions. After oral administration, mean total VPA concentrations in plasma were significantly higher in the morning than in the evening during the absorption phase. C max tended to be higher, t max was shorter (P < 0.05) and absorption rate constant (ka) tended to be larger (0.05 < P < 0.1) for VPA in the morning than in the evening, although no difference was demonstrated in other pharmacokinetic values between morning and evening trials. After rectal administration, no significant difference was demonstrated in VPA kinetics between morning and evening trials. The rectal administration might have an advantage to eliminate the time‐dependent changes of VPA kinetics. Thus the current practice of giving a rectal dose seems to be justified because the time‐dependent changes in VPA kinetics observed after oral administration may be reduced without compromising therapeutic efficacy.