CHRONOPHARMACOKINETICS OF VALPROIC ACID FOLLOWING CONSTANT-RATE ADMINISTRATION IN MICE AND INFLUENCE OF FEEDING SCHEDULE

AIM: To study the circadian rhythm in pharmacokinetics of valproic aci d (VA) and influence of feeding schedule on the rhythm. METHODS: Sodiu m valproate was administered by osmotic minipump technique (1.062 mg . h(-1)) and iv (50 mg . kg(-1)) to ICR mice fed under ad lib or time-r estricted schedules to determine the time-dependent changes of VA kine tics. RESULTS: Plasma VA concentration and clearance at steady-state s howed circadian rhythms (P < 0.01). Time-restricted feeding influenced the rhythm of VA kinetics, acrophases of rhythms shifted approximatel y 12 h. CONCLUSION: timing of dosing is important for VA kinetics and feeding schedule is one of synchronizers in VA kinetics.