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Keywords:

  • Dog;
  • Pharmacokinetics;
  • Renal failure

The pharmacokinetics of benazepril, enalapril, and their active metabolites (benazeprilat and enalaprilat) were compared after a single administration of each product by the oral route at the recommended dosage (0.5 mg/kg for both drugs) in the dog before and after moderate experimental renal impairment. Ten dogs were randomly assigned to 2 groups of 5 animals in a 2-period crossover design for angiotensin-converting enzyme inhibitor administration. Renal failure was surgically induced by right ne-phrectomy and electrocoagulation of the remaining kidney. Renal mass reduction induced a significant decrease (P < .001) in glomerular filtration rate (GFR) (1.7 ± 0.3 versus 3.3 ± 0.7 mL/kg/minute). No significant differences before and after surgery were observed for enalapril and benazepril kinetics. The area under the curve (AUC) for enalaprilat increased after surgery from 23.6 ± 14.7 to 42.4 ± 20.9 μg-minute/mL (P < .01). Mean peak plasma concentration (Cmax) was increased in the impaired dogs (59.1 ± 23.3 versus 43.9 ± 32.9 ng/mL), but this variation was not significant (P > .05). Renal failure had no significant effect on AUC for benazeprilat (13.8 ± 9.8 versus 14.9 ± 5.0 μg-minute/mL) (P > .05), but Cmax decreased significantly (from 55.0 ± 26.4 to 31.9 ± 17.7 ng/mL) (P < .05). Multiple regression analysis showed that both GFR and AUC for enalapril were highly significant variables that explained the variation in AUC for enalaprilat (R2= .86, P < .001) but not for benazeprilat (R2= .12, P > .05). The results of this study indicate that exposure to enalaprilat, but not to benazeprilat, is increased in dogs with subclinical renal impairment.