Chronopharmacokinetics of valproic acid following constant-rate administration in mice and influence of feeding schedule.
OBJECTIVE
To study the circadian rhythm in pharmacokinetics of valproic acid (VA) and influence of feeding schedule on the rhythm.


METHODS
Sodium valproate was administered by osmotic minipump technique (1.062 mg.h-1) and i.v. (50 mg.kg-1) to ICR mice fed under ad lib or time-restricted schedules to determine the time-dependent changes of VA kinetics.


RESULTS
Plasma VA concentration and clearance at steady-state showed circadian rhythms (P < 0.01). Time-restricted feeding influenced the rhythm of VA kinetics, acrophases of rhythms shifted approximately 12 h.


CONCLUSIONS
Timing of dosing is important for VA kinetics and feeding schedule is one of synchronizers in VA kinetics.
Song
J G
JG
Department of Pharmacology, Ehime University School of Medicine, Japan.
Ohdo
S
S
Ogawa
N
N
D000818:Animals; D002940:Circadian Rhythm; D004334:Drug Administration Schedule; D005247:Feeding Behavior; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008813:Mice, Inbred ICR; D014635:Valproic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*
D014635:Valproic Acid