Absorption
Depakene is quickly absorbed when taken by mouth. The delay that occurs when it is taken with food is not important during long-term treatment, but it could have some effect when treatment is first begun. Without food, peak levels in the blood are reached in approximately 2 hours for both capsules and syrup. With food, reaching the peak level takes approximately 4 hours.

Distribution and metabolism
Valproate is highly bound (90%) to proteins in the blood. Thus, only 10% is free or unbound and able to enter the brain. However, as the blood level rises above 80 micrograms per milliliter (mcg/mL) to 100 mcg/mL, the proportion of valproic acid that is free (and thus available to the brain) can rise markedly. Free blood and brain levels of valproic acid can range from 7% to 28% of the total levels. Since the free level is what the brain "sees," at levels over approximately 90 mcg/mL, there can be a fairly dramatic increase in the brain levels. For example, a person with a total level of 75 mcg/mL may have a free blood and brain level of 7.5 mcg/mL (10%), but when the level is 130 mcg/mL, the blood and brain levels may increase to 20.8 mcg/mL (16%). This increase could be associated with improvement in seizure control and worsening of side effects in the body and brain.

More than 95% of valproate is broken down in the liver by several different metabolic pathways. Many metabolites are produced, and some of them have longer half-lives than the original drug. Some metabolites may contribute to the efficacy and side effects. The half-life ranges from 8 to 16 hours, with shorter times in children and longer times in the elderly.

The differences between peak and trough levels can be marked. In some cases the peak level is more than double the trough level. Because this medication is metabolized in the liver, Depakene should not be administered to patients with hepatic disease or significant hepatic dysfunction.

Steady state
In children, steady state is reached after about 2 days of taking a stable dose of Depakene. It takes about 5 days for the same thing to happen in seniors. After steady state is achieved, the levels of medication in the blood can be expected to be fairly constant. The dose that a patient takes should not be increased until steady state has been reached (or some time later), so that the effects of the previous dose can be assessed.