Physiological modelling of renal drug clearance

A physiological model of renal drug clearance is presented with the aim of establishing a basis for adjusting drug dosing regimens in renal insufficiency. In agreement with the morphology of blood supply to the nephron, the model assumes serial arrangement of the processes involved in drug excretion. Fractional extraction by filtration in the glomeruli is defined in terms of the product of the unbound fraction of the drug, the filtration fraction being responsible for the limited extraction efficiency of this process. For a description of the limitations of the tubular secretory process by plasma flow through peritubular capillaries, the parallel tube model is utilized. The assumption of direct proportionality between the transport maximum of the secretory process and filtrate flow in the tubules permits a quantitative comparison of the intrinsic tubular secretion clearance and the effectiveness of the filtration process. Provided that the secretory mechanism is highly effective, renal clearance becomes dependent only on kidney plasma flow and the fraction of drug not reabsorbed in the tubules. Tubular reabsorption results only in a proportional decrease in renal clearance.