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A general empirical model for renal drug handling in pharmacokinetic analyses
Author(s) -
Wright Daniel F. B.,
Duffull Stephen B.
Publication year - 2017
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13306
Subject(s) - nephron , renal function , clearance , drug , urology , function (biology) , metabolic clearance rate , pharmacokinetics , kidney , medicine , endocrinology , pharmacology , biology , evolutionary biology
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.