title: Study on glutathionesulfonic acid sodium salt as biodistribution promoter for thiopental sodium.
abstract: The effects of glutathione (GSH) and glutathionesulfonic acid sodium salt [N-(N-gamma-L-glutamyl-L-beta-sulfoalanyl)glycine sodium salt, GSO3Na], which is a minor metabolite of GSH, on the pharmacokinetics of thiopental sodium were investigated in rats. The concomitant use of GSO3Na with thiopental sodium significantly increased the tissue-to-plasma concentration ratio (Kp) 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 Kp value of thiopental sodium 5 min after its administration with concomitant GSO3Na decreased significantly only in the spleen. Neither GSO3Na 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 GSO3Na but not by GSH. This phenomenon seemed to be concerned with a mechanism to increase the Kp 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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Okayama University, Japan.
authors.forename: Yuhsuke
authors.initials: Y
authors.lastname: Ohkawa
authors.forename: Tomonori
authors.initials: T
authors.lastname: Fujimoto
authors.forename: Kyohko
authors.initials: K
authors.lastname: Higashiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maeda
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Asoh
authors.forename: Masateru
authors.initials: M
authors.lastname: Kurumi
authors.forename: Kenji
authors.initials: K
authors.lastname: Sasaki
authors.forename: Taiji
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D019540:Area Under Curve; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000097:blood / Q000493:pharmacokinetics*; D007202:Indicators and Reagents; D008297:Male; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D013056:Spectrophotometry, Ultraviolet; D013268:Stimulation, Chemical; D013874:Thiopental / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D006993:Hypnotics and Sedatives; D007202:Indicators and Reagents; C469714:glutathionesulfonic acid sodium salt; D005978:Glutathione; D013874:Thiopental