Average parameters as a trend to reduce the residual variability in bioequivalence trials.
Bioavailability and bioequivalence evaluations of drug products carried out using the experimental maximum concentration (Cmax) and the experimental time to reach Cmax (Tmax), are not advisable for slow-release formulations and for trials performed with saliva as biologic fluid. When slow-release curves are considered the drug concentration profiles usually show multiple peaks, making it difficult to compute a Cmax,Tmax value. The saliva profile throughout time shows a high variability observed as more than one peak in the saliva concentration versus time curves. In both cases, even if there is a major peak, when the statistical analysis of the data is performed, an important variability in Cmax results in high values in the residual variance of the ANOVA test. Consequently, the power of the bioequivalence test decreases and sometimes it is not possible to conclude on bioequivalence. The average concentration (Cav), the average maximum concentration (Cmax,av) and Cmax,av/Cav x 100 (%Cmax,av) are proposed in this paper as possible parameters in order to evaluate the profile of the concentration-time curves, as they reduce the residual variability in bioequivalence studies.
Fagiolino
P
P
Department of Pharmacology and Biopharmacy, Faculty of Chemistry, Montevideo, Uruguay.
Vazquez
M
M
D000704:Analysis of Variance; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations; D006801:Humans; D015233:Models, Statistical; D012463:Saliva / Q000378:metabolism; D013810:Therapeutic Equivalency
D003692:Delayed-Action Preparations