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Evaluation of glomerular filtration rate estimation by means of plasma clearance of iohexol in domestic rabbits (Oryctolagus cuniculus)

Ilaria Lippi DVM, PhD1, Francesca Perondi DVM, PhD1, Daniele Petrini DVM1, Maria Cristina La Fortuna DVM1, Giacomo Luci PharmD, PhD1, Luigi Intorre DVM, PhD1, Grazia Guidi DVM, PhD1, and Valentina Meucci PharmD, PhD1
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  • 1 1Department of Veterinary Science, Faculty of Veterinary Medicine, University of Pisa, Pisa, PI 56122 Italy.

Abstract

OBJECTIVE

To evaluate glomerular filtration rate (GFR) estimation by means of plasma clearance of iohexol (IOX) in domestic rabbits and to assess accuracy of limited-sampling models for GFR estimation.

ANIMALS

6 healthy domestic rabbits (Oryctolagus cuniculus).

PROCEDURES

Each rabbit received IOX (64.7 mg/kg [0.1 mL/kg], IV), and blood samples were collected at predetermined times before and after administration. Plasma IOX concentration was determined by high-performance liquid chromatography. The pharmacokinetics of IOX was determined by a noncompartmental method. For each rabbit, plasma clearance of IOX was determined by dividing the total IOX dose administered by the area under the concentration-time curve indexed to the subject's body weight. The GFR estimated from the plasma IOX concentration at 6 sampling times (referent model) was compared with that estimated from the plasma IOX concentration at 5 (model A), 4 (model B), and 3 (models C, D, and E) sampling times (limited-sampling models).

RESULTS

Mean ± SD GFR was 4.41 ± 1.10 mL/min/kg for the referent model and did not differ significantly from the GFR estimated by any of the limited-sampling models. The GFR bias magnitude relative to the referent model was smallest for model D in which GFR was estimated from plasma IOX concentrations at 5, 15, and 90 minutes after IOX administration.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested that plasma clearance of IOX was a safe, reliable, accurate, and clinically feasible method to estimate GFR in domestic rabbits. Further research is necessary to refine the method.

Abstract

OBJECTIVE

To evaluate glomerular filtration rate (GFR) estimation by means of plasma clearance of iohexol (IOX) in domestic rabbits and to assess accuracy of limited-sampling models for GFR estimation.

ANIMALS

6 healthy domestic rabbits (Oryctolagus cuniculus).

PROCEDURES

Each rabbit received IOX (64.7 mg/kg [0.1 mL/kg], IV), and blood samples were collected at predetermined times before and after administration. Plasma IOX concentration was determined by high-performance liquid chromatography. The pharmacokinetics of IOX was determined by a noncompartmental method. For each rabbit, plasma clearance of IOX was determined by dividing the total IOX dose administered by the area under the concentration-time curve indexed to the subject's body weight. The GFR estimated from the plasma IOX concentration at 6 sampling times (referent model) was compared with that estimated from the plasma IOX concentration at 5 (model A), 4 (model B), and 3 (models C, D, and E) sampling times (limited-sampling models).

RESULTS

Mean ± SD GFR was 4.41 ± 1.10 mL/min/kg for the referent model and did not differ significantly from the GFR estimated by any of the limited-sampling models. The GFR bias magnitude relative to the referent model was smallest for model D in which GFR was estimated from plasma IOX concentrations at 5, 15, and 90 minutes after IOX administration.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested that plasma clearance of IOX was a safe, reliable, accurate, and clinically feasible method to estimate GFR in domestic rabbits. Further research is necessary to refine the method.

Contributor Notes

Address correspondence to Dr. Lippi (ilariausa@gmail.com).