Study on Glutathionesulphonic Acid as Biodistribution Promoter: Concomitant Use Effect on Verapamil Hydrochloride and Tegafur

Abstract

The effect of glutathionesulphonic acid (N-(N-γ-L-glutamyl-L-β-sulphoalanylglycine, GSO₃H), which is one of the minor metabolites of glutathione (GSH), on the pharmacokinetics of verapamil hydrochloride (verapamil·HCl) and tegafur was investigated in rats. GSO₃H was concomitantly used as sodium salt (GSO₃Na). No significant change by the concomitant use of GSO₃Na was recognized in the pharmacokinetics parameters of verapamil·HCl and tegafur, and plasma elimination of both substances was not affected by GSO₃Na. The tissue-to-plasma concentration ratio (K_p) of verapamil·HCl in the lung 5 min after its administration under concomitant use of GSO₃Na rose significantly, however, this effect disappeared 120 min after administration. No significant change was recognized in other organs. On the other hand, a significant difference of K_p of tegafur under a steady state concentration of GSO₃Na was not recognized in any organs. It seemed that the elevation of a lipid solubility (oil water partition coefficient) of verapamil·HCl by the concomitant use of GSO₃Na was related to the increase of the K_p value of verapamil·HCl in the lung. The partition coefficient of GSO₃Na itself decreased when it was used concomitantly with verapamil·HCl.