Pharmacokinetics of tolbutamide after oral administration in rabbits with folate-induced renal failure.
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.
Bae
Hak Yeon
HY
College of Medicine, Chosun University, Kwangju 501-759, Korea.
Choi
Dong Hyun
DH
Choi
Jun Shik
JS
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*
D007004:Hypoglycemic Agents; D005492:Folic Acid; D014044:Tolbutamide