An experimental model for pharmacokinetic analysis in renal failure

A renal failure model was developed in the dog to evaluate the effect of varying degrees of renal failure on drug pharmacokinetics. A controlled impairment of renal function was induced by electrocoagulating portions of one kidney and excising the contralateral kidney. The magnitude of renal dysfunction, defined by the percentage of normal glomerular filtration rate (% NGFR), was estimated by125I-iothalamate total body clearance. The model was evaluated by comparing the pharmacokinetics of oxytetracycline (OTC) before and after the induction of renal failure in two experiments: single intraveneous dose (11dogs); single intravenous and oral doses (8dogs). Renal failure (RF) was studied in three classes according to % NGFR: <25%,severe RF; 25–39%,moderate RF; and ≥ 40%,mild RF. Significant reductions were observed over RF class in OTC pharmacokinetic parameters for elimination and distribution but not for oral absorption.