Pharmacokinetics and pharmacodynamics of ramipril and ramiprilat after intravenous and oral doses of ramipril in healthy horses.
Authors: Serrano-Rodríguez J M, Gómez-Díez M, Esgueva M, Castejón-Riber C, Mena-Bravo A, Priego-Capote F, Serrano Caballero J M, Muñoz A
Journal: Veterinary journal (London, England : 1997)
Summary
# Editorial Summary: Ramipril Pharmacokinetics in Horses Ramipril, an ACE inhibitor commonly used in human cardiovascular medicine, remains understudied in equine patients despite potential applications in managing hypertension and certain cardiac conditions. Serrano-Rodríguez and colleagues administered ramipril intravenously (0.050 mg/kg) and orally (0–0.80 mg/kg) to six healthy horses in a crossover study, measuring serum ramipril and its active metabolite ramiprilat using LC-MS/MS, whilst simultaneously tracking serum ACE activity and blood pressure responses. Although oral bioavailability of ramiprilat was disappointingly low at 6–9%, the oral formulation demonstrated dose-dependent ACE suppression, reaching 84.27% maximum inhibition at the highest dose (0.80 mg/kg) compared with just 27.68% at 0.050 mg/kg; intravenous administration achieved near-complete inhibition at 98.88%. Critically, systemic blood pressure remained unchanged throughout all treatments, suggesting that healthy horses may not show haemodynamic responses to ACE inhibition despite effective enzymatic suppression. These findings indicate that whilst oral ramipril requires relatively high doses to achieve meaningful ACE inhibition in horses, sufficient enteral absorption and bioconversion occurs to warrant further investigation in clinical populations, particularly animals with hypertension or cardiac pathology where ACE inhibition may confer therapeutic benefit.
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Practical Takeaways
- •If using ramipril orally in horses, doses of at least 0.80 mg/kg are needed to achieve substantial ACE inhibition; lower doses (0.05-0.40 mg/kg) provide suboptimal inhibition
- •Oral ramipril can be effective in equine patients despite low bioavailability of the active metabolite, as the drug converts adequately in the body
- •Blood pressure monitoring may not be necessary during ramipril therapy in healthy horses, as hemodynamic changes were not observed
Key Findings
- •Systemic bioavailability of ramiprilat after oral ramipril administration was only 6-9% in horses
- •Intravenous ramipril at 0.050 mg/kg achieved 98.88% maximum ACE inhibition from baseline
- •Oral ramipril at 0.80 mg/kg produced 84.27% ACE inhibition despite low bioavailability, indicating sufficient enteral absorption and bioconversion
- •Blood pressure remained unchanged throughout all treatment phases, suggesting systemic hemodynamic stability