Study on glutathionesulphonic acid as biodistribution promoter: Concomitant use effect on verapamil hydrochloride and tegafur

The effect of glutathionesulphonic acid (N-(N-gamma -L-glutamyl-L-beta -sul phoalanylglycine, GSO(3H)), which is one of the minor metabolites of glutat hione (GSH), on the pharmacokinetics of verapamil hydrochloride (verapamil . HCl) and tegafur was investigated in rats. CSO3H was concomitantly used a s sodium salt (GSO(3)Na). No significant change by the concomitant use of GSO(3)Na was recognized in the pharmacokinetics parameters of verapamil . HCl and tegafur, and plasma elimination of both substances was not affected by GSO(3)Na. The tissue-to- plasma concentration ratio (K-p) of verapamil . HCl in the lung 5 min after its administration under concomitant use of GSO(3)Na rose significantly, h owever, this effect disappeared 120 min after administration. No significan t change nas recognized in other organs. On the other hand, a significant d ifference of K-p of tegafur under a steady state concentration of GSO(3)Na was not recognized in any organs. It seemed that the elevation of a lipid s olubility (oil water partition coefficient) of verapamil . HCl by the conco mitant use of GSO(3)Na was related to the increase of the K-p value of vera pamil . HCI in the lung. The partition coefficient of GSO(3)Na itself decre ased when it was used concomitantly with verapamil HCl.