QUANTITATIVE-ANALYSIS OF DRUG HANDLING BY THE KIDNEY USING A PHYSIOLOGICAL MODEL OF RENAL DRUG CLEARANCE

Published data on the renal clearance of creatinine, p-aminohippuric a cid (PAH) and kanamycin in relation to glomerular filtration rate (GFR ) in patients with various renal diseases were analysed by a physiolog ical model of renal clearance. Fitting of the data by the general line ar equation representing the model proposed by Levy [10] resulted in i nsignificant intercepts with the ordinate, indicating the unsuitabilit y of the model for the detection of tubular secretory activity. Use of this model also did not lead to significant improvement in goodness o f fit compared to simple proportionality of renal clearance and GFR. O n the other hand, parameter estimates of the physiological model obtai ned from the data by nonlinear regression analysis revealed statistica lly significant tubular secretion both of PAH and creatinine. The much lower tubular secretory activity estimated from the kanamycin data di d not reach statistical significance. For compounds exhibiting statist ically significant tubular secretion, use of the physiologically based relationship between renal clearance and GFR significantly improved t he goodness of fit to the data as compared to simple proportionality o f both variables. It is concluded that analysis of the relationship be tween renal clearance of drugs and GFR using the physiological model o f renal clearance can contribute to our knowledge of drug handling by the kidney, and may facilitate drug classification according to total extraction by this organ.