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Comparison of pharmacokinetic variables for creatinine and iohexol in dogs with various degrees of renal function

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  • 1 Unité de recherche clinique, Institut national polytechnique de Toulouse, Université de Toulouse, F-31076 Toulouse, France.
  • | 2 Department of Companion Animal Clinical Sciences, Norwegian School of Veterinary Science, Oslo, Norway.
  • | 3 Unité de recherche clinique, Institut national polytechnique de Toulouse, Université de Toulouse, F-31076 Toulouse, France.
  • | 4 Unité de recherche clinique, Institut national polytechnique de Toulouse, Université de Toulouse, F-31076 Toulouse, France.
  • | 5 Unité de recherche clinique, Institut national polytechnique de Toulouse, Université de Toulouse, F-31076 Toulouse, France.
  • | 6 Ecole nationale vétérinaire de Toulouse, Institut national polytechnique de Toulouse, Université de Toulouse, F-31076 Toulouse, France.
  • | 7 Unité mixte de recherches 1331, Institut national de la recherche agronomique, Toxalim, F-31027 Toulouse, France.
  • | 8 Unité de recherche clinique, Institut national polytechnique de Toulouse, Université de Toulouse, F-31076 Toulouse, France.
  • | 9 Department of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, Oslo, Norway.
  • | 10 Unité de recherche clinique, Institut national polytechnique de Toulouse, Université de Toulouse, F-31076 Toulouse, France.
  • | 11 Unité de recherche clinique, Institut national polytechnique de Toulouse, Université de Toulouse, F-31076 Toulouse, France.
  • | 12 Department of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, Oslo, Norway.
  • | 13 Research Center, Royal Canin SAS, 30470 Aimargues, France.
  • | 14 Unité de recherche clinique, Institut national polytechnique de Toulouse, Université de Toulouse, F-31076 Toulouse, France.

Abstract

Objective—To compare pharmacokinetics and clearances of creatinine and iohexol as estimates of glomerular filtration rate (GFR) in dogs with various degrees of renal function.

Animals—50 Great Anglo-Francais Tricolor Hounds with various degrees of renal function.

Procedures—Boluses of iohexol (40 mg/kg) and creatinine (647 mg/kg) were injected IV. Blood samples were collected before administration and 5 and 10 minutes and 1, 2, 4, 6, and 8 hours after administration. Plasma creatinine and iohexol concentrations were assayed via an enzymatic method and high-performance liquid chromatography, respectively. A noncompartmental approach was used for pharmacokinetic analysis. Pharmacokinetic variables were compared via a Bland-Altman plot and an ANOVA.

Results—Compared with results for creatinine, iohexol had a significantly higher mean ± SD plasma clearance (3.4 ± 0.8 mL/min/kg vs 3.0 ± 0.7 mL/min/kg) and a significantly lower mean volume of distribution at steady state (250 ± 37 mL/kg vs 539 ± 73 mL/kg), mean residence time (80 ± 31 minutes vs 195 ± 73 minutes), and mean elimination half-life (74 ± 20 minutes vs 173 ± 53 minutes). Despite discrepancies between clearances, especially for high values, the difference was < 0.6 mL/min/kg for 34 (68%) dogs. Three dogs with a low GFR (< 2 mL/min/kg) were classified similarly by both methods.

Conclusions and Clinical Relevance—Plasma iohexol and creatinine clearances can be used interchangeably for screening patients suspected of having chronic kidney disease (ie, low GFR), but large differences may exist for dogs with a GFR within or above the reference range.

Abstract

Objective—To compare pharmacokinetics and clearances of creatinine and iohexol as estimates of glomerular filtration rate (GFR) in dogs with various degrees of renal function.

Animals—50 Great Anglo-Francais Tricolor Hounds with various degrees of renal function.

Procedures—Boluses of iohexol (40 mg/kg) and creatinine (647 mg/kg) were injected IV. Blood samples were collected before administration and 5 and 10 minutes and 1, 2, 4, 6, and 8 hours after administration. Plasma creatinine and iohexol concentrations were assayed via an enzymatic method and high-performance liquid chromatography, respectively. A noncompartmental approach was used for pharmacokinetic analysis. Pharmacokinetic variables were compared via a Bland-Altman plot and an ANOVA.

Results—Compared with results for creatinine, iohexol had a significantly higher mean ± SD plasma clearance (3.4 ± 0.8 mL/min/kg vs 3.0 ± 0.7 mL/min/kg) and a significantly lower mean volume of distribution at steady state (250 ± 37 mL/kg vs 539 ± 73 mL/kg), mean residence time (80 ± 31 minutes vs 195 ± 73 minutes), and mean elimination half-life (74 ± 20 minutes vs 173 ± 53 minutes). Despite discrepancies between clearances, especially for high values, the difference was < 0.6 mL/min/kg for 34 (68%) dogs. Three dogs with a low GFR (< 2 mL/min/kg) were classified similarly by both methods.

Conclusions and Clinical Relevance—Plasma iohexol and creatinine clearances can be used interchangeably for screening patients suspected of having chronic kidney disease (ie, low GFR), but large differences may exist for dogs with a GFR within or above the reference range.

Contributor Notes

Dr. Queau's present address is Research Center, Royal Canin SAS, 30470 Aimargues, France.

Dr. Craig's present address is Department of Small Animal Medicine, Faculty of Veterinary Science, University of Sydney, Sydney, NSW 2006, Australia.

Supported by Royal Canin SAS and the Norwegian Research Council.

Presented in abstract form at the 27th Annual Forum of the American College of Veterinary Internal Medicine, Montréal, June 2009.

The authors thank Claude Germain for assistance with the plasma creatinine assays.

Address correspondence to Dr. Lefebvre (h.lefebvre@envt.fr).