This study was conducted in order to assess the bioequivalence of a test and reference tablet formulation containing 10 mg of ramipril ((1S,5S,7S)-8-[(2S)-2-[[(1S)-1-ethoxycarbonyl-3-phenyl-propyl]amino]propanoyl] -8-azabicyclo[3.3.0]octane-7-carboxylic acid, CAS 87333-19-5). Forty healthy male and female volunteers were treated in a single-centre randomised, single-dose, open-label, 2-way crossover study, with a washout period of 35 days between treatments. Plasma samples were collected up to 168 h post-dosing for the determination of ramipril and its active metabolite, ramiprilat, by LC-MS/MS. The evaluation of bioequivalence was based on the following pharmacokinetic parameters that were calculated by standard non-compartmental methods: the area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration (AUCt) and that extrapolated to infinity (AUC) and the maximum observed concentration (C max). The 90% confidence interval of the ratios (test/reference) (obtained by analysis of variance, ANOVA) were 0.83-1.20 for Cmax of ramipril, 0.90-1.10 for Cmax of ramiprilat, 0.95-1.23 for AUC 0-48 of ramipril, 0.97-1.11 for AUC0-168 of ramiprilat, 0.96-1.23 for AUC of ramipril and 0.98-1.15 for AUC of ramiprilat, i. e. within the predefined acceptable range for the conclusion of bioequivalence. T max of the test formulation was 0.67 ± 0.33 h for ramipril and 2.28 ± 0.74 h for ramiprilat; Tmax of the reference formulation was 0.71 ± 0.32 h for ramipril and 2.40 ± 0.88 for ramiprilat. The ramipril and ramiprilat Tmax values estimated for the test and the reference formulations were not significantly different (p-value > 0.05). The study indicated that the test and reference formulations containing 10 mg of ramipril were equivalent in terms of both the rate and extent of bioavailability.

Bioequivalence study of two tablet formulations of ramipril in healthy volunteers

BUCCI, Marco;TONIATO, ELENA;MEZZETTI, Andrea;MARTINOTTI, Stefano;
2009-01-01

Abstract

This study was conducted in order to assess the bioequivalence of a test and reference tablet formulation containing 10 mg of ramipril ((1S,5S,7S)-8-[(2S)-2-[[(1S)-1-ethoxycarbonyl-3-phenyl-propyl]amino]propanoyl] -8-azabicyclo[3.3.0]octane-7-carboxylic acid, CAS 87333-19-5). Forty healthy male and female volunteers were treated in a single-centre randomised, single-dose, open-label, 2-way crossover study, with a washout period of 35 days between treatments. Plasma samples were collected up to 168 h post-dosing for the determination of ramipril and its active metabolite, ramiprilat, by LC-MS/MS. The evaluation of bioequivalence was based on the following pharmacokinetic parameters that were calculated by standard non-compartmental methods: the area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration (AUCt) and that extrapolated to infinity (AUC) and the maximum observed concentration (C max). The 90% confidence interval of the ratios (test/reference) (obtained by analysis of variance, ANOVA) were 0.83-1.20 for Cmax of ramipril, 0.90-1.10 for Cmax of ramiprilat, 0.95-1.23 for AUC 0-48 of ramipril, 0.97-1.11 for AUC0-168 of ramiprilat, 0.96-1.23 for AUC of ramipril and 0.98-1.15 for AUC of ramiprilat, i. e. within the predefined acceptable range for the conclusion of bioequivalence. T max of the test formulation was 0.67 ± 0.33 h for ramipril and 2.28 ± 0.74 h for ramiprilat; Tmax of the reference formulation was 0.71 ± 0.32 h for ramipril and 2.40 ± 0.88 for ramiprilat. The ramipril and ramiprilat Tmax values estimated for the test and the reference formulations were not significantly different (p-value > 0.05). The study indicated that the test and reference formulations containing 10 mg of ramipril were equivalent in terms of both the rate and extent of bioavailability.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11564/220404
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