Pharmacokinetics of a valpromide isomer, valnoctamide, in dogs

Valnoctamide (2-ethyl-3-methylpentanamide; VCD), an isomer of valpromide possessing both anxiolytic and antiepileptic properties, has been used as a tranquilizer in the treatment of anxiety and tension. As VCD is an isomer of valpromide (VPD), which is used both as an antiepileptic and an antipsychotic agent, we wanted to ascertain whether any differences in their pharmacological activity could be explained by pharmacokinetics. The pharmacokinetics of VCD have been studied in dogs following iv and oral administration (400 mg). Following iv administration, VCD was rapidly distributed and plasma levels declined in a biphasic fashion. The mean terminal half-life of VCD was 1.9 +/- 0.5 h and the total body clearance was 3.0 +/- 0.8 L/h. This clearance value, after normalization to blood clearance, was only approximately 10% of the hepatic blood flow. This fact indicates that the extraction ratio (E) of VCD by the liver is low, and that this drug has a restrictive clearance. The volume of distribution of VCD was within the value of the total body water. Following oral administration, the absolute bioavailability of VCD was 94 +/- 14%, and the terminal half-life was similar to that obtained after iv administration. The absolute bioavailability value thus shows that, upon oral administration, VCD is completely absorbed and does not undergo a first-pass effect. The pharmacokinetics of VCD was shown to be similar to that of VPD. The major difference was that VCD was completely absorbed and was not biotransformed to its homologous acid.