Truncated area under the curve: an alternative approach to assess the bioequivalence of long half-life drugs
- Autores: Susana Marques de Almeida
- Directores de la Tesis: Ignasi Gich Saladich (dir. tes.)
- Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2011
- Idioma: español
- Materias:
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- Resumen
Data from eight single dose, randomized, open-label, crossover bioequivalence studies was used to compare the results obtained by the traditional method and by the truncated AUC approach.
The test and reference formulations were administered under fasting conditions and blood samples were obtained up to several times, depending on the specific pharmacokinetic properties of the substances. Plasma concentrations were determined and AUCs were obtained by non-compartmental analysis. Statistical comparison was accomplished using ANOVA. In all but one study, the 90% confidence intervals (90%CI) were all within the limits of acceptance of bioequivalence (80.00-125.00%) for the parameters obtained by the standard approach of bioequivalence analysis (AUClast and AUCinf) and for those resulting from the alternative truncation approach (AUCt). Truncation times varied according to specific pharmacokinetic characteristics of the drug but AUC72 was considered to be the most relevant truncation time, for reasons outlined in this thesis.
These results indicate that truncated AUCs is a valid approach for the assessment of bioequivalence of the studied drugs given that it has led to the same conclusions as the conventional approach, while involving several advantages (ethical, logistical and economical).
