Document Detail


The nucleotide derivatives inosine and inosinic acid inhibit intestinal absorption of mizoribine in rats.
MedLine Citation:
PMID:  16438959     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Makoto Okada; Kimihiro Suzuki; Masahiro Nakashima; Takashi Nakanishi; Noriyasu Fujioka
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Publication Detail:
Type:  Journal Article     Date:  2006-01-24
Journal Detail:
Title:  European journal of pharmacology     Volume:  531     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-13     Completed Date:  2006-04-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  140-4     Citation Subset:  IM    
Affiliation:
Internal Medicine I, National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama, 359-8513, Japan. grd1804@ndmc.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Area Under Curve
Chromatography, High Pressure Liquid
Dose-Response Relationship, Drug
Immunosuppressive Agents / pharmacokinetics
Inosine / pharmacology*
Inosine Monophosphate / pharmacology*
Intestinal Absorption / drug effects*
Male
Metabolic Clearance Rate
Rats
Rats, Sprague-Dawley
Ribonucleosides / blood,  pharmacokinetics*,  urine
Chemical
Reg. No./Substance:
0/Immunosuppressive Agents; 0/Ribonucleosides; 131-99-7/Inosine Monophosphate; 50924-49-7/bredinin; 58-63-9/Inosine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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