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.


CONCLUSIONS
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.
Mendes
G Duarte
GD
Department of Internal Medicine, State University of Campinas, SP, Brazil.
Dantas Sanfelice
A T
AT
do Carmo Borges
N C
NC
Cavedal
L E
LE
Sverdloff
C
C
Prado Galuppo
M
M
Módolo
J H
JH
De Nucci
G
G
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D017257:Ramipril / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D012016:Reference Values; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013810:Therapeutic Equivalency; D013997:Time Factors
D000959:Antihypertensive Agents; C052549:ramiprilat; D017257:Ramipril