Absorption
Valproic acid is rapidly absorbed in the GI tract. Divalproex dissociates into valproic acid in the GI tract. T max is 4 to 17 h (extended-release [ER] tablets).

Distribution
Vd of total or free valproic acid is 11 and 92 L per 1.73 m 2 , respectively. 80% to 90% protein bound (concentration-dependent).

Metabolism
Metabolized primarily in the liver.

Elimination
30% to 50% excreted as glucuronide conjugate in the urine. The t ½ is 9 to 16 h for valproate.

Special Populations
Renal Function Impairment
Protein binding in renal failure patients is substantially reduced.

Hepatic Function Impairment
Cl may be decreased and unbound fraction of valproate may be increased.

Elderly
Intrinsic Cl is reduced 39%; the free fraction is increased 44%.

Alcohol, CNS depressants
Enhanced CNS depression.

Amitriptyline/Nortriptyline, barbiturates, diazepam, ethosuximide, hydantoins (eg, phenytoin), phenobarbital, primidone, zidovudine
Plasma levels of these drugs may be increased.

Carbamazepine
Carbamazepine plasma levels may be decreased while carbamazepine-10,11-epoxide levels may be increased; decreased valproic acid levels.

Charcoal, cholestyramine, meropenem, rifampin
May decrease valproic acid levels.

Chlorpromazine, cimetidine, erythromycin, felbamate, fluoxetine, salicylates
May increase valproic acid levels.

Clonazepam
Absence status may be induced in patients with a history of absence type seizures.

Lamotrigine
Decreased valproic acid levels; increased lamotrigine levels.

Lorazepam
Lorazepam plasma levels may be increased.

Olanzapine
Risk of hepatic adverse reactions may be increased; olanzapine levels may be decreased.

Topiramate
Coadministration with valproic acid has been associated with hyperammonemia with and without encephalopathy. Plasma levels of both drugs may be decreased.

Warfarin
Warfarin may be displaced from its protein binding site, transiently increasing the anticoagulant effect.

1.對本藥過敏者

2.嚴重肝疾病患者

3.本品服用期間請勿併服Carbapenem系抗生素