Interaction Between Thiopentone and Sodium Valproate

Abstract

The effect of sodium valproate on the binding of thiopentone to serum protein was studied in vitro. In the absence of valproate the unbound fraction of thiopentone was 15.2 +/- 0.64%, but with concentrations of valproic acid in excess of the therapeutic range, it increased to 22.42 +/- 1.65%. Scatchard plots for thiopentone in the absence and presence of valproate were investigated also. The barbiturate was bound by one group of binding sites with the association constant, Ka = 2.81 X 10(3) litre mol-1 and the number of binding sites (n) = 2.3. There was a marked decrease in this association constant in the presence of valproic acid (Ka = 1.82 X 10(3) litre mol-1), but without significant change in the number of binding sites (n = 2.13). Additionally, the effect of administration of sodium valproate i.v. on thiopentone anaesthesia was examined in rabbits. The recovery time from thiopentone was markedly longer in the presence of the anticonvulsant drug (17.0 min v. 37.1 min).

The Role of Unbound Drug in Pharmacokinetics/Pharmacodynamics and in Therapy

“…In spite of these warnings, studies in the 70's continued in vitro particularly concerned with the significance of interactions at the three binding sites of the albumin molecule [2]. Under this light, although changes in the fu had already been observed under certain physiopathological or therapeutic circumstances, rarely the influence to the pharmacological response in vivo was addressed [3][4][5].…”