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Current Topics in Pharmacology   Volumes    Volume 22 
Replicate evaluation of drug exposure to study bioequivalence between two brands of phenytoin in patients
Natalia Guevara, Pietro Fagiolino, Marta Vázquez, Cecilia Maldonado
Pages: 55 - 61
Number of pages: 7
Current Topics in Pharmacology
Volume 22 

Copyright © 2018 Research Trends. All rights reserved

Two multisource phenytoin products (Antepil® and Comitoína®) available for oral administration in Uruguay were authorized to continue in the market provided they could demonstrate similar pattern of efficacy and safety. To accomplish this, fifty-seven epileptic patients under chronic treatment with one of the two brands were enrolled in a bioequivalence parallel design study in which saliva concentration-time profiles of phenytoin were evaluated twice in each subject. Maximum and mean steady state concentrations (Cmax and Css) and peak trough fluctuation (PTF) were obtained from the saliva concentration-time profiles. Two 90% confidence intervals (90%CI) for the ratio of the geometric brand means were calculated for each parameter using the total and the residual variance. The results show a narrower 90%CI when the residual instead of the total variance is used, making it possible to include the 90%CI obtained from the residual variance within the bioequivalence interval [0.80-1.25], in opposition to the wider 90%CI obtained from the total variance for the parameters Css and Cmax. Regarding PTF, as the residual variability was similar to the total one, none of the 90%CI could be included within the bioequivalence interval. However, for parameters with high intrinsic coefficient of variation, a wider bioequivalence interval has been accepted by the WHO. The results obtained in this study allow us to conclude that Antepil® and Comitoina® are bioequivalent. Moreover, the procedure of parallel assay, with replicate evaluation of drug exposure, should be considered as a valuable solution to demonstrate bioequivalence of multisource drug products.
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