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The urinary excretion of ramipril, ramiprilat, and their metabolites is reduced in patients with impaired renal function. Compared to normal subjects, patients with creatinine clearance less than 40 ml/ min/ 1.73m 2 had higher peak and trough ramiprilat levels and slightly longer times to peak concentrations. (See DOSAGE AND ADMINISTRATION.) In patients with impaired liver function, the metabolism of ramipril to ramiprilat appears to be slowed, pos-sibly because of diminished activity of hepatic esterases, and plasma ramipril levels in these patients are increased about 3-fold. Peak concentrations of ramiprilat in these patients, however, are not different from those seen in subjects with normal hepatic function, and the effect of a given dose on plasma ACE activity does not vary with hepatic function. Pharmacodynamics Text Continues Below
Single doses of ramipril of 2.5Ð 20 mg produce approximately 60Ð 80% inhibition of ACE activity 4 hours after dosing with approximately 40Ð 60% inhibition after 24 hours. Multiple oral doses of ramipril of 2.0 mg or more cause plasma ACE activity to fall by more than 90% 4 hours after dosing, with over 80% inhibition of ACE activ-ity remaining 24 hours after dosing. The more prolonged effect of even small multiple doses presumably reflects saturation of ACE binding sites by ramiprilat and relatively slow release from those sites. Pharmacodynamics and Clinical Effects Reduction in Risk of Myocardial Infarction, Stroke, and Death from Cardiovascular Causes The Heart Outcomes Prevention Evaluation study (HOPE study) was a large, multi-center, randomized, place-bo controlled, 2x2 factorial design, double-blind study conducted in 9,541 patients (4,645 on ALTACE) who were 55 years or older and considered at high risk of developing a major cardiovascular event because of a history of coronary artery disease, stroke, peripheral vascular disease, or diabetes that was accompanied by at least one other cardiovascular risk factor (hypertension, elevated total cholesterol levels, low HDL levels, cigarette smoking, or documented microalbuminuria). Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
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