Kinetic studies on drug disposition in rabbits. III. Effect of tolbutamide on renal excretion of sulfamethizole.
The effect of tolbutamide (TB) on the urinary excretion of sulfamethizole (SMZ) under constant infusion of SMZ at 100 mg/h was studied. Intravenous administration of TB (50 mg/kg) caused a decrease in the urinary excretion rate of SMZ but an increase in the unbound concentration of SMZ in plasma. The total concentration of SMZ in plasma decreased rapidly after TB injection and then increased gradually to a level higher than the control. The slope of the terminal phase of the unbound concentration of TB in plasma in the presence of SMZ was significantly smaller than that of TB alone. The analysis using the perfusion limited model showed that the elimination kinetics of SMZ in the presence of TB could be described by the mutual displacement of plasma protein binding of both drugs and the competitive inhibition of the tubular secretion of SMZ by the unbound concentration of TB in renal vein. Further the inhibitor constant was in good agreement with that for the in vitro uptake by renal cortex slices.
Katayama
K
K
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Ohtani
H
H
Mizuno
H
H
Taniguchi
T
T
Kakemi
M
M
Koizumi
T
T
D000818:Animals; D004347:Drug Interactions; D008954:Models, Biological; D011817:Rabbits / Q000378:metabolism*; D013419:Sulfamethizole / Q000493:pharmacokinetics* / Q000652:urine; D013432:Sulfathiazoles / Q000493:pharmacokinetics*; D014044:Tolbutamide / Q000494:pharmacology*
D013432:Sulfathiazoles; D013419:Sulfamethizole; D014044:Tolbutamide