Bioequivalence of Acenocoumarol in Chilean Volunteers: an Open, Randomized, Double-Blind, Single-Dose, 2-Period, and 2-Sequence Crossover Study for 2 Oral Formulations

J. Sasso; P. Carmona; L. Quiñones; M. Ortiz; E. Tamayo; N. Varela; D. Cáceres; I. Saavedra

doi:10.1055/s-0032-1316290

Arzneimittelforschung, Table of Contents

Arzneimittelforschung 2012; 62(08): 395-399
DOI: 10.1055/s-0032-1316290

Original Article

Bioequivalence of Acenocoumarol in Chilean Volunteers: an Open, Randomized, Double-Blind, Single-Dose, 2-Period, and 2-Sequence Crossover Study for 2 Oral Formulations

J. Sasso

¹Center of Pharmacological and Toxicological Research (IFT), Molecular and Clinical Pharmacology Program, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile

,

P. Carmona

¹Center of Pharmacological and Toxicological Research (IFT), Molecular and Clinical Pharmacology Program, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile

,

L. Quiñones

¹Center of Pharmacological and Toxicological Research (IFT), Molecular and Clinical Pharmacology Program, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile

,

M. Ortiz

¹Center of Pharmacological and Toxicological Research (IFT), Molecular and Clinical Pharmacology Program, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile

²Department of Cardiology, University of Chile Clinical Hospital, Santiago, Chile

,

E. Tamayo

¹Center of Pharmacological and Toxicological Research (IFT), Molecular and Clinical Pharmacology Program, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile

,

N. Varela

¹Center of Pharmacological and Toxicological Research (IFT), Molecular and Clinical Pharmacology Program, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile

³School of Medical Technology, Faculty of Medicine, University of Chile, Santiago, Chile

,

D. Cáceres

¹Center of Pharmacological and Toxicological Research (IFT), Molecular and Clinical Pharmacology Program, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile

⁴School of Public Health, Faculty of Medicine, Epidemiology Division, University of Chile, Santiago, Chile

,

I. Saavedra

¹Center of Pharmacological and Toxicological Research (IFT), Molecular and Clinical Pharmacology Program, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile

› Author Affiliations

Abstract

The aim of this study was to compare the bioavailability of an oral formulation of the coumarin derivative-vitamine K antagonist acenocoumarol (Acebron^TM 4 mg, Test) with the reference formulation (Neo-Sintrom^TM 4 mg). We performed a single-dose, double-blind, fasting, 2-period, 2-sequence, crossover study design. Plasma concentrations of acenocoumarol were determined using a validated UPLC-MS/MS method. 24 healthy Chilean volunteers (11 male, 13 female) were enrolled and all of them completed the study. Adverse events were monitored throughout the study. The values of the pharmacokinetic parameters were (mean ± SD): AUC_0-24 =1 364.38±499.26 ngxh/mL for the test and 1 328.39±429.20 ngxh/mL for the reference; AUC_0-∞ =1 786.00±732.85 ngxh/mL for the test and 1 706.71±599.66 ngxh/mL for the reference; C_max =180.69±35.11 ng/mL with a T_max of 1.83±0.95 h for the test and 186.97±38.21 ng/mL with a T_max of 2.19±0.83 h for the reference. Regarding half life measurements, the mean ± SD of t_1/2 were 11.84±4.54 h for the test and 11.08±3.28 h for the reference. The 90% confidence intervals for the test/reference ratio using logarithmic transformed data were 97.89–100.87%, 98.62–101.99% and 98.64–102.38% for C_max, AUC_0-t(24) and AUC_0–∞. There were no significant differences in pharmacokinetic parameters between groups.

The results obtained in this study lead us to conclude, based on FDA criteria, that the test acenocoumarol formulation (Acebron^TM, 4 mg tablets) is bioequivalent to the reference product (Neo-Sintrom^TM, 4 mg tablets).

Key words

therapeutic equivalence - pharmacokinetics - pharmaceutics anticoagulant - drug regulation

Full Text

References

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