Study on glutathionesulfonic acid sodium salt as biodistribution promoter for thiopental sodium

The effects of glutathione (GSH) and glutathionesulfonic acid sodium salt [N-(N-γ-L-glutamyl-L-β-sulfoalanyl)glycine sodium salt, GSO ₃Na], which is a minor metabolite of GSH, on the pharmacokinetics of thiopental sodium were investigated in rats. The concomitant use of GSO ₃Na with thiopental sodium significantly increased the tissue-to-plasma concentration ratio (K_p) of thiopental sodium 60 min after its administration in the heart, lung, brain, liver, kidney, and spleen, while GSH did not affect them. On the other hand, the K_p value of thiopental sodium 5 min after its administration with concomitant GSO ₃Na decreased significantly only in the spleen. Neither GSO ₃Na nor GSH changes the pharmacokinetic parameters of thiopental sodium. Significant change of the binding ratio of thiopental sodium to bovine serum albumin (BSA) was not observed by the addition of less than 5-fold GSO₃Na. About 50% of thiopental sodium was bound to the brain, lung or liver, however, no significant change of this binding ratio was observed by the concomitant use of GSO₃Na. The partition coefficient of thiopental sodium apparently increased by the concomitant use of GSO ₃Na but not by GSH. This phenomenon seemed to be concerned with a mechanism to increase the K_p values of thiopental sodium in the tissues. The increment in the drug distribution to tissues with concomitant GSO₃Na observed in this study is useful information for the application of drug combinations as a biodistribution promoter.