THE PHARMACOKINETICS OF [14C]‐EDROPHONIUM IN NORMAL WISTAR RATS AND HOMOZYGOUS GUNN RATS WITH LIGATED RENAL PEDICLES

Abstract

1 The distribution kinetics of [¹⁴C]-edrophonium were studied in both normal Wistar and homozygous Gunn rats with ligated renal pedicles. 2 After intravenous injection the plasma concentration-time curve of [¹⁴C]-edrophonium was adequately fitted by a triexponential function in both species of rat and interpreted in terms of a three compartment model. 3 The influence of the route of administration (i.e., systemic venous versus hepatic portal) of [¹⁴C]-edrophonium on its concentration in plasma was studied in normal Wistar rats with ligated renal pedicles. There was a marked difference in the area under the plasma concentration-time curve depending on the route of administration. 4 The parameters of the model were determined and compared. 5 The value of the metabolism rate constant was approximately the same in both species of rat. This suggests that the rate of conjugation of [¹⁴C]-edrophonium is unaltered in the homozygous Gunn rat despite the genetic lesion in UDP-glucuronyltransferase.