Effect of iodopyracet on renal excretion of sulfamethizole in rabbits.
To predict quantitatively drug interaction kinetics from the single-drug clearance studies, we examined the effect of iodopyracet (IOD) on sulfamethizole (SMZ) excretion in rabbits. Even though the decline of systemic IOD plasma concentration was linear, the renal clearance of SMZ decreased significantly in the presence of IOD. The results could be described by a perfusion model incorporated with the competitive inhibition for tubular secretion. For IOD with a high extraction ratio, it was suggested that a heavy load of the drug was supplied to the sites of secretion and caused the saturation of transport systems, even though the renal excretion kinetics were apparently linear in respect to the systemic circulation. These facts indicated that a linear relationship between the concentrations in the systemic circulation and at the sites of tubular secretion can not always be presumed. Consequently, SMZ-IOD interaction study stressed the importance of the drug concentrations at the sites of interaction for quantitative elucidation of drug-drug interactions.
Katayama
K
K
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Tsubota
E
E
Endoh
M
M
Kakemi
M
M
Koizumi
T
T
D000818:Animals; D004347:Drug Interactions; D066298:In Vitro Techniques; D007468:Iodopyracet / Q000494:pharmacology*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008954:Models, Biological; D011817:Rabbits; D013419:Sulfamethizole / Q000493:pharmacokinetics*; D013432:Sulfathiazoles / Q000493:pharmacokinetics*
D013432:Sulfathiazoles; D013419:Sulfamethizole; D007468:Iodopyracet