A general empirical model for renal drug handling in pharmacokinetic analyses

Dose adjustment in renal insufficiency is generally based on the assumption that renal drug clearance is related linearly to glomerular filtration rate. The theory underpinning this model is the intact nephron hypothesis, which says that impaired renal function is caused by a reduction in the number of complete (intact) nephrons. The purpose of the present commentary is to propose a general empirical model for renal drug handling. We will explore models for renal function under two scenarios: one that aligns with the intact nephron hypothesis, and one that relaxes the assumptions of this hypothesis. We propose that a nonlinear, non-intact nephron model will allow for differences in renal drug handling, while incorporating the intact nephron hypothesis model as a special case.