Keywords: pharmacokinetics, pharmacogenetics, bioequivalence, biostatistics, variability
Room: Wilson A
Massive analysis of genetic variants nowadays is allowing healthcare professionals to take the personalized pharmacological therapy and precision medicine from the bench to the bedside. On this same track, the objective of the present roundtable is to discuss the biological variability given by genetic factors to apply them in bioequivalence and comparative bioavailability studies for generic product testing, ultimately to control within-subject and between-subject variation. Moreover, this discussion intends to gather experiences that genetics of participating volunteers in this type of trials is relevant and that it is possible to extrapolate this knowledge to pharmacological practice in real patients in a near future. As a proof-of-concept on the roundtable issue, we will discuss an experience after Fluoxetine Hydrochloride administration in a bioequivalence study with additional genotyping in 24 participant healthy volunteers, in where genetic variants were analyzed and statistically correlated with the clinical and pharmacological variables (primary pharmacokinetics and elimination-phase data). Exploratory analysis spotlighted metabolizing enzymes variants, and more than 60 different genotypes were interesting after this selection, and its pharmacokinetic phenotypes were associated and studied. After statistical testing, subjects could be classified according to its metabolic profile for Fluoxetine and this was confirmed with the genetic information obtained, demonstrating the usefulness of the genetic profiling for bioequivalence studies when subjects’ genetic idiosyncrasy could be relevant or wanted to be explored. Future perspectives on this research line are to continue studying phenotype-genotype relationship with the information retrieved in controlled trials, to be able to relate more polymorphisms with pharmacokinetic phenotypes for several drugs of volunteers participating in this type of studies in relevant and refined statistical models.