title: Hypoglycemic action and disposition of gliclazide in normal and analbuminemic rats.
abstract: The hypoglycemic action and disposition of gliclazide, an oral antidiabetic drug, was investigated in normal and analbuminemic rats. Orally administered gliclazide exhibited a stronger hypoglycemic action in analbuminemic rats than in normal rats. However, the plasma concentration of the drug in the mutant was much lower than that in the normal. This apparent discrepancy may be clarified by measuring the plasma concentration of unbound gliclazide. Analbuminemic rats gave larger values for the total body clearance and steady state volume of distribution of gliclazide than normal rats. The biliary and urinary excretion rates of radioactivity after intravenous bolus administration of [3H]-gliclazide were much greater in the mutant than in the normal. The binding of gliclazide to serum in analbuminemic rats was much lower than that in normal rats. Furthermore, the radioactivities of some tissues after oral administration of [3H]-gliclazide were found to be significantly higher in the mutant than in the normal. These results clearly indicate that albumin plays an important role in the hypoglycemic activity and disposition of gliclazide in rats.
authors.affiliation: Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Imamura
authors.forename: K
authors.initials: K
authors.lastname: Kimachi
authors.forename: S
authors.initials: S
authors.lastname: Nagase
authors.forename: M
authors.initials: M
authors.lastname: Otagiri
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D005907:Gliclazide / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000652:urine; D007408:Intestinal Absorption; D008297:Male; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000172:deficiency* / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D001786:Blood Glucose; D012709:Serum Albumin; D005907:Gliclazide