Comparative bioavailability of two ramipril formulations after single-dose administration in healthy volunteers.

OBJECTIVE: To assess the bioequivalence of a ramipril 5 mg tablet formulation (ramipril test formulation from Laboratórios Biosintética Ltda (Sao Paulo, Brazil) and Triatec from Aventis Pharma (Sueano, Brazil) standard reference formulation) in 26 healthy volunteers of both sexes. METHODS: The study was conducted using an open, randomized, 2-period crossover design with a 2-week washout interval. Plasma samples were obtained over a 36-hour period. Plasma ramipril and ramiprilat concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reaction monitoring (MRM). From the ramipril and ramiprilat plasma concentration vs. time curves, the following pharmacokinetic parameters were obtained: AUClast, AUCinf and Cmax. RESULTS: The limit of quantification was 0.2 ng x ml(-1) and 1.0 ng x ml(-1) for ramipril and ramiprilat, respectively. The geometric means and 90% confidence intervals (CI) for Ramipril/Triatec and Ramiprilat/Triatec percent ratios were: 104.69% (90% CI = 93.21-117.59%) for Cmax, 102.49% (90% CI = 92.76-113.24%) for AUClast, 103.60% (90% CI = 93.56 114.73%) for AUCinf, 108.48% (90% CI = 98.86-119.03%) for Cmax, 105.88% (90% CI = 101.55-110.39%) for AUClast, 97.30% (90% CI = 90.17-104.99%) for AUCinf, respectively. CONCLUSION: Since the 90% CI for AUClast, AUCinf and Cmax ratios were within the 80-125% interval proposed by the U.S. FDA, it was concluded that the ramipril formulation produced by Laboratórios Biosintética Ltda is bioequivalent to the Triatec formulation in both rate and extent of absorption.

Ramipril vs espironolactona en el remodelamiento ventricular izquierdo post-infarto: estudio randomizado y doble ciego / Ramipril vs spironolactone in the left ventricular remodeling after infarction: randomized and double blind study

Patients and methods: Patients hospitalized for a first episode of acute myocardial infartion were blindly and randomly assigned to receive ramipril (2.5 mg bid), spironolactone (25 mg bid) or placebo. Ejection fraction, left ventricular en diastolic and end systolic volumes were measured by multigated radionuclide angiography, at baseline and after six months of treatment. Results: Twenty four patients were assigned to placebo, 31 to ramipril and 23 to spironolactone. Age, gender; Killip class, treatment with thrombolytics, revascularization procedures and use of additional medications were similar in the three groups. After six months of treatment, efection fraction increased from 34,5 ñ 2,3 to 4,2 ñ 2,4 percent in patients on ramipril, from 32,6 ñ 2,9 to 36,6 ñ 2,7 percent in patients on spironolactone, and decreased from 37 ñ 3 to 31 ñ 3 in patients on placebo (ANOVA between gropus p < 0.05). Basal end systolic volumen was similar in all three gropus, increased from 43,4 ñ 3,4 to 61,4 ñ 6,0 ml/m2 in patients on placebo and did not change in patients on spironolactone or ramipril (ANOVA p < 0.05). End diastolic volume was also similar in the three groups, increased from 70,6 ñ 4,3 to 92,8 ñ 6,4 ml/m2 in patients on placebo and did no change with the other treatments. Conclusions: Ramipril and spironolactone had similar effects on ventricular remodeling after acute myocardial infaction, suggesting that aldosterone contributes to this phenomenon and that inhibition of its receptor may be as effective as ACE inhibition in its prevention

Cambios morfofuncionales precoces en el infarto del miocardio experimental: efecto de la inhibición de la enzima convertidora de angiotensina / Morphofunctional early changes in myocardial experimental infarction: effect of angiotensin converting enzyme inhibition

El presente estudio tuvo como objetivo caracterizar el efecto de un inhibidor de la enzima convertidora de angiotensina (ECA) sobre los cambios estructurales y funcionales miocárdicos post infarto al miocardio (IAM) experimental en ratas. Se evaluaron los cambios morfológicos y las propiedades mecánicas del miocardio en el corazón aislado perfundido. El estudio se efectuó en dos grupos experimentales, uno tratado con placebo (n = 22) y otro administrando el inhibidor de ECA ramipril (10 mg/l en agua a beber, n = 15) durante 45 días. Al comparar con el grupo placebo, en el grupo tratado con ramipril observamos menor relación peso ventricular derecho/peso corporal (0.83 ñ 0.38 vs 1.16 ñ 0.31, respectivamente, p < 0.05), mayor espesor de la pared ventricular izquierda en la zona de la cicatriz del infarto (0.89 ñ 0.58 vs 0.57 ñ 0.28 mm, respectivamente, p < 0.05) y una menor pendiente de la relación tensión-elongación diastólica (106.8 ñ 0.9 vs 13.7 ñ 1.2 g/cm², respectivamente, p < 0.05). El porcentaje del área ocupado por el infarto fue 39.4 ñ 12.1 en el grupo placebo y 34.8 ñ 13.4 en el grupo tratado con ramipril (ns). En conclusión, el inhibidor de la ECA ramipril, a las dosis utilizadas durante 6 semanas en ratas con infarto al miocardio experimental, demostró prevenir el desarrollo de hipertrofia ventricular derecha, con el desarrollo de una cicatriz de mayor grosor y un VI menos rígido con una tendencia a un menor tamaño del infarto que en las ratas no tratadas.Estos efectos morfofuncionales podrían explicar en parte el efecto benéfico de los inhibidores de la ECA en el curso clínico del IAM

Eficacia clínica y aceptabilidad de ramipril en el tratamiento de la hipertensión arterial esencial etapas 1 y 2: resultados de un estudio multicéntrico / Clinical effectiveness and tolerance of ramipril in the treatment of essential arterial hypertension level 1 and 2: results of a multicentric study

One hundred eighty eight hyoertensive patients, aged 21 to 80 years old, coming from 4 Chilean hospitals were studied. Using an open non controlled design, they were treated with placebo for two weeks and with the active drug during eight weeks, in initial doses of 2.5 mg/day that were adjusted to 5 mg/day in diastolic blood pressure did not drop below 90 mm Hg or if its reduction was less than 10 mm Hg. During the active drug treatment period, systolic blood pressure decreased from 164.8ñ7.2 to 147.3ñ4.8 mm Hg. Diastolic blood pressure dropped from 102.3ñ3.1 to 87.8ñ3.0 mm Hg. Seventy percent of patients achieved a diastolic blood pressure of less than 90 mm Hg, 56.9 percent with 2.5 mg/day and 13.8 percent with 5 mg/day. Dizziness, cough and headache were the main adverse reactions, observed in 3.7, 3.2 and 2.1 percent of patients respectively. Adherence to treatment was 98 percent. There were no changes in laboratory values during the treatment period. Ramipril is effective and well tolerated in the treatment of essential hypertension