Effect of renal insufficiency on the pharmacokinetics and pharmacodynamics of benazepril in cats.
The effect of renal insufficiency was studied on the pharmacokinetics (PK) and pharmacodynamics (PD) of the angiotensin-converting enzyme (ACE) inhibitor benazepril in cats. The active metabolite of benazepril, benazeprilat, is eliminated principally ( approximately 85%) via biliary excretion in cats. A total of 20 control animals and 32 cats with moderate renal insufficiency induced by partial nephrectomy were used. Assessments were made at steady state after treatment with placebo or benazepril (0.25-2 mg/kg) once daily for a minimum of 10 days. The PK endpoint was the AUC (0-->24 h) of total plasma benazeprilat. The PD endpoints were systolic, diastolic and mean blood pressures (respectively SBP, DBP and MBP) measured by telemetry, and plasma ACE activity, assessed by an ex vivo assay. Renal function was assessed by glomerular filtration rate (GFR), measured by inulin clearance, and plasma creatinine concentrations (1/PCr). As compared with control animals, the renal insufficient cats had a 78% reduction in GFR (0.57 +/- 0.41 mL/min kg), increased plasma creatinine (2.7 +/- 1.0 mg/dL), urea (44.0 +/- 11.9 mg/dL) and ACE activity, and moderately increased blood pressure (SBP 171.8 +/- 5.1 mmHg) (all parameters P < 0.05). Renal insufficient cats receiving benazepril had significantly (P < 0.05) lower SBP, DBP, MBP and ACE, and higher GFR values as compared with placebo-treated animals. There were no significant differences in SBP, DBP, MBP, benazeprilat or ACE values according to the degree of renal insufficiency in cats receiving benazepril. It is concluded that no dose adjustment of benazepril is necessary in cats with moderate renal insufficiency.
King
J N
JN
Novartis Animal Health Inc., Basel, Switzerland. jonathan.king@ah.novartis.com
Strehlau
G
G
Wernsing
J
J
Brown
S A
SA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000652:urine; D000818:Animals; D019540:Area Under Curve; D001552:Benzazepines / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D002371:Cat Diseases / Q000378:metabolism*; D002415:Cats / Q000378:metabolism*; D003404:Creatinine / Q000097:blood; D005260:Female; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D008297:Male; D051437:Renal Insufficiency / Q000378:metabolism / Q000662:veterinary*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D003404:Creatinine; C052133:benazeprilat; C044946:benazepril