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Pharmacological particulars
Pharmacotherapeutic group: Cardiovascular system, ACE inhibitor, benazepril. ATCvet code: QC09AA07
Pharmacodynamic properties
Benazepril hydrochloride is a prodrug hydrolysed in vivo to its active metabolite, benazeprilat.
Benazeprilat is a highly potent and selective inhibitor of ACE, thus preventing the conversion of inactive angiotensin I to active angiotensin II and thereby also reducing synthesis of aldosterone. Therefore, it blocks effects mediated by angiotensin II and aldosterone, including vasoconstriction of both arteries and veins, retention of sodium and water by the kidney and remodelling effects (including pathological cardiac hypertrophy and degenerative renal changes).
The product causes long-lasting inhibition of plasma ACE activity in cats, with more than 95% inhibition at peak effect and significant activity (>90%) persisting 24 hours after dosing.
In cats with experimental renal insufficiency, the product normalized the elevated glomerular capillary pressure and reduced the systemic blood pressure.
Reduction in glomerular hypertension may retard the progression of kidney disease by inhibition of further damage to the kidneys. Placebo controlled clinical field studies in cats with chronic kidney disease (CKD) have demonstrated that the product significantly reduced levels of urine protein and urine protein to creatinine ratio (UPC); this effect is probably mediated via reduced glomerular hypertension and beneficial effects on the glomerular basement membrane.
No effect of the product on survival in cats with CKD has been shown, but the product increased the appetite of the cats, particularly in more advanced cases
Pharmacokinetic properties
After oral administration of benazepril hydrochloride, peak levels of benazepril are attained rapidly (Tmax 2 hours) and decline quickly as the active substance is partially metabolised by liver enzymes to benazeprilat. The systemic bioavailability is incomplete due to incomplete absorption (<30% in cats) and first pass metabolism.
Peak benazeprilat concentrations (Cmax of 110.0 ng/ml after a dose of 0.65 mg/kg benazepril hydrochloride) are achieved with a Tmax of 1 hour and half.
Benazeprilat concentrations decline biphasically: the initial fast phase (t1/2=2.4 hours) represents elimination of free drug, while the terminal phase (t1/2=29 hours) reflects the release of benazeprilat that was bound to ACE, mainly in the tissues.
Benazepril and benazeprilat are extensively bound to plasma proteins (85-90%), and in tissues are found mainly in the liver and kidney.
Repeated administration of the product leads to slight bioaccumulation of benazeprilat (R=1.36 with 0.5 mg/kg), steady state being achieved within a few days.
Benazeprilat is excreted 85% via the biliary and 15% via the urinary route. The clearance of benazeprilat is not affected in cats with impaired renal function and therefore no adjustment of the product dose is required in cases of renal insufficiency.