title: The nucleotide derivatives inosine and inosinic acid inhibit intestinal absorption of mizoribine in rats.
abstract: Inosine is absorbed via a N1 transporter that is selective for purine nucleosides. It is conceivable that inosine and inosinic acid might affect the intestinal absorption of mizoribine, an imidazole nucleoside that inhibits the de novo production pathway of guanine ribonucleotide. An in situ loop experiment was performed using four intestinal loop segments prepared by ligation: segment 1, about 6 to 9 cm from the end of the pylorus; segment 2, about 10 to 13 cm; segment 3, about 14 to 17 cm; and segment 4, about 18 to 21 cm. Mizoribine (0.1 mg/ml) or mizoribine+inosine (1 or 10 mg/ml) were infused into each loop. The absorption rate in the most proximal segment of intestinal loop was the highest. In the presence of inosine, this rate decreased significantly. Urinary recovery rates of mizoribine were significantly decreased by pretreatment with inosine or inosinic acid. The Cmax in the group given mizoribine+inosinic acid was significantly lower than that in the group given mizoribine alone. These results strongly indicate that (I) the N1 transporter in the intestine might act to absorb mizoribine; and (II) inosine and inosinic acid might competitively inhibit the absorption of mizoribine via the N1 transporter.
authors.affiliation: Internal Medicine I, National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama, 359-8513, Japan. grd1804@ndmc.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Okada
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakashima
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Fujioka
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics; D007288:Inosine / Q000494:pharmacology*; D007291:Inosine Monophosphate / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D017207:Rats, Sprague-Dawley; D012263:Ribonucleosides / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D007166:Immunosuppressive Agents; D012263:Ribonucleosides; D007291:Inosine Monophosphate; C010052:mizoribine; D007288:Inosine