Measurement of glomerular filtration rate and effective renal plasma flow in the conscious beagle dog by single intravenous bolus of iohexol and p-aminohippuric acid

The objective of this study was to validate a kinetic approach for the simu ltaneous measurement of glomerular filtration rate (GFR) and effective rena l plasma flow (ERPF) in the dog. Six healthy male Beagle dogs were randomly assigned in a three-period cross-over study of intravenous bolus administr ation of iohexol (64.7 mg/kg). PAH (10 mg/kg), and an iohexol/PAH mixture. PAH and iohexol were determined simultaneously by a validated high-performa nce liquid chromatographic method. The iohexol and PAH data obtained after intravenous administration were analyzed using noncompartmental and bicompa rtmental approaches. A simplified iohexol plasma clearance was also calcula ted from the terminal elimination phase of the plasma iohexol concentration s versus time profile. The total plasma clearance values for PAH and exo-io hexol were 13 +/- 2.3 mL/kg/min and 2.9 +/- 0.3 mL/kg/min, respectively. No significant (or biologically relevant) effect of coadministration of PAH a nd iohexol was observed on the pharmacokinetic parameters of either drug. T he calculation of simplified plasma clearance led to an overestimation of t he true plasma clearance. In conclusion, GFR and ERPF can easily and rapidl y be measured in the dog by this approach which is relatively noninvasive. (C) 1999 Elsevier Science Inc.