DP-VPA : Antiepileptic drug

Valproic acid (VPA) is an effective antiepileptic drug that has been on the market for over 30 years. It suffers, however, from significant dose-dependent adverse effects that limit its use. DP-VPA, a new chemical entity, is a lipid-modified VPA that exhibits superior potency in animal models of epilepsy. DP-VPA is subject to selective pathology-related activation by phospholipase A 2 (PLA 2 ), an enzyme that is upregulated in firing neurons. DP-VPA has undergone extensive preclinical testing in animals that confirmed its efficacy in chemical and genetic epilepsy models at doses up to 80-fold lower than for the parent drug VPA. DP-VPA is absorbed mainly via the lymphatic route and does not undergo first-pass hepatic metabolism. DP-VPA's pharmacokinetic and pharmacodynamic characteristics should enable once-daily dosing and improved patient compliance. Safety studies in healthy human volunteers and epilepsy patients indicate that DP-VPA is well tolerated. In patients with resistant epilepsy, DP-VPA has a marked effect on seizure frequency and is well tolerated. It provides VPA serum concentrations below the accepted therapeutic range, which results in fewer adverse effects during treatment with DP-VPA. DP-VPA is thus a promising new alternative to VPA for the treatment of epilepsy, with potential also for the treatment of bipolar disorder and migraine.