Urine flow dependence of renal clearance and interrelation of renal reabsorption and physicochemical properties of drugs.
A physiologically based model is presented for the analysis of the reabsorption kinetics of drugs in the renal tubules. The two reabsorption parameters, AR(I) X Pe and sigma, expressing the permeability of a drug through lipoidal membranes and the reflection coefficient, respectively, are obtained on the basis of this model using the results of clearance experiments in rats. These two reabsorption parameters are compared among four drugs, sulfanilamide, sulfamethizole, theophylline, and ethanol. Urine flow dependence of the percentage of reabsorbed drugs is reasonably expressed by the model. Moreover, the percentage of reabsorbed drugs which are highly reflected at the membranes is affected by the change of the glomerular filtration rate. In contrast, the percentage of reabsorbed drugs, such as ethanol, having a small reflection coefficient is not sensitive to the glomerular filtration rate. A good linear relationship is obtained between AR(I) X Pe and the n-octanol/water partition coefficient. The reflection coefficient is related to the molecular weight of the compound. The reflection coefficient of ethanol is small because of its low molecular weight, whereas the reflection coefficient is almost unity when the molecular weight is higher than 170. Accordingly, this physiological model approach can be acceptable to the reabsorption kinetics of drugs in the renal tubules.
Komiya
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D000042:Absorption; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D000431:Ethanol / Q000378:metabolism*; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D051381:Rats; D011919:Rats, Inbred Strains; D013419:Sulfamethizole / Q000378:metabolism*; D000077145:Sulfanilamide; D013424:Sulfanilamides / Q000378:metabolism*; D013432:Sulfathiazoles / Q000378:metabolism*; D013806:Theophylline / Q000378:metabolism*; D014563:Urodynamics
D013424:Sulfanilamides; D013432:Sulfathiazoles; D000077145:Sulfanilamide; D013419:Sulfamethizole; D000431:Ethanol; D013806:Theophylline