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-sulphoalanylglycine, GSO3H), which is one of the minor metabolites of glutathione (GSH), on the pharmacokinetics of verapamil hydrochloride (verapamil x 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 x HCl and tegafur, and plasma elimination of both substances was not affected by GSO3Na. The tissue-to-plasma concentration ratio (Kp) of verapamil x 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 Kp 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 x HCl by the concomitant use of GSO3Na was related to the increase of the Kp value of verapamil x HCl in the lung. The partition coefficient of GSO3Na itself decreased when it was used concomitantly with verapamil x HCl.
Ohkawa
Y
Y
Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Higashiyama
K
K
Sugaya
S
S
Asoh
T
T
Maeda
H
H
Sasaki
K
K
Nakayama
T
T
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000493:pharmacokinetics*; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005978:Glutathione / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D005641:Tegafur / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution / Q000187:drug effects; D014700:Verapamil / Q000737:chemistry / Q000493:pharmacokinetics*
D000964:Antimetabolites, Antineoplastic; D002121:Calcium Channel Blockers; D005641:Tegafur; C040136:glutathione sulfonate; D014700:Verapamil; D005978:Glutathione