Clinical pharmacology of valpromide

Valpromide has been used as an antiepileptic and antipsychotic drug for the past 25 years in several European countries. Unlike its corresponding acid, valproic acid, whose pharmacokinetics have been quite extensively reviewed, and despite years of clinical use, it appears that no reviews have been written on the pharmacokinetics of valpromide. This article summarises and analyses its pharmacokinetics from various aspects, with a special emphasis on the differences between valpromide and valproic acid. In humans, valpromide is a prodrug of valproic acid. Despite their chemical similarity, the pharmacokinetics of the 2 drugs in humans are quite distinct. Compared with valproic acid. valpromide has a very short half-life (mean +/- SD: 0.84 +/- 0.33h; n = 6), a high clearance value (70 +/- 31 L/h) and a large volume of distribution (75 +/- 13L). Despite its rapid biotransformation to valproic acid, valpromide has some special characteristics, such as its inhibition of the enzyme epoxide hydrolase which is responsible for the metabolism of carbamazepine-10, 11-epoxide. This review discusses the pharmacokinetics of valpromide, the interactions between it and other drugs such as carbamazepine and amitriptyline, and its antiepileptic and antipsychotic activities.