title: Pharmacokinetics of tolbutamide after oral administration in rabbits with folate-induced renal failure.
abstract: The pharmacokinetic changes of tolbutamide were studied after oral administration to normal rabbits and mild and medium folate-induced renal failure rabbits. Tolbutmide 50 mg/kg was orally administered to the rabbits. The plasma concentrations of tolbutamide were significantly increased (p<0.05) at 9 to 24 hr in mild and medium folate-induced renal failure rabbits compared with those in normal rabbits. Therefore, the area under the plasma concentration-time curves (AUC) was significantly higher (p<0.05 and p<0.01 respectively) in mild and medium folate-induced renal failure rabbits (2906 microg/ml x hr and 4074 microg/ml x hr) than that in normal rabbits (2295 microg/ml x hr). The cumulative urinary excretion of tolbutamide was significantly decreased (p<0.05) in medium folate-induced renal failure rabbits (3.3 mg) compared with the normal rabbits (5.9 mg). The elimination rate constant (Kel) of tolbutamide was significantly slower in medium folate-induced renal failure rabbits (0.027 hr(-1)) than that in normal rabbits(0.044 hr(-1)). The terminal half-life of tolbutamide in medium folate-induced renal failure rabbits (25.5 hr) was significantly longer (p<0.01) than in normal rabbits (15.7 hr). These results could be considered as possibly due to inhibited excretion of tolbutamide metabolites or retarded metabolism of tolbutamide.
authors.affiliation: College of Medicine, Chosun University, Kwangju 501-759, Korea.
authors.forename: Hak Yeon
authors.initials: HY
authors.lastname: Bae
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Choi
authors.forename: Jun Shik
authors.initials: JS
authors.lastname: Choi
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000378:metabolism*; D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D005492:Folic Acid; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism; D011817:Rabbits; D012044:Regression Analysis; D013056:Spectrophotometry, Ultraviolet; D014044:Tolbutamide / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D007004:Hypoglycemic Agents; D005492:Folic Acid; D014044:Tolbutamide