Use of pharmacogenetics in bioequivalence studies to reduce sample size: an example with mirtazapine and CYP2D6
| Autor: | Francisco Abad-Santos, Adrián LLerena, Nicolás González-Vacarezza, Pedro Dorado, Francisco E Estévez-Carrizo, Eva M Peñas-Lledó, A Carcas-Sansuan |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
CYP2D6 Genotype Mirtazapine Mianserin Antidepressive Agents Tricyclic Bioequivalence Pharmacology law.invention Randomized controlled trial Pharmacokinetics law Genetics Humans Medicine Cross-Over Studies business.industry Crossover study Healthy Volunteers Biopharmaceutical Cytochrome P-450 CYP2D6 Therapeutic Equivalency Pharmacogenetics Sample size determination Sample Size Molecular Medicine Female business |
| Zdroj: | The Pharmacogenomics Journal. 13:452-455 |
| ISSN: | 1473-1150 1470-269X |
| DOI: | 10.1038/tpj.2012.29 |
| Popis: | In bioequivalence studies, intra-individual variability (CV(w)) is critical in determining sample size. In particular, highly variable drugs may require enrollment of a greater number of subjects. We hypothesize that a strategy to reduce pharmacokinetic CV(w), and hence sample size and costs, would be to include subjects with decreased metabolic enzyme capacity for the drug under study. Therefore, two mirtazapine studies, two-way, two-period crossover design (n=68) were re-analysed to calculate the total CV(w) and the CV(w)s in three different CYP2D6 genotype groups (0, 1 and ≥ 2 active genes). The results showed that a 29.2 or 15.3% sample size reduction would have been possible if the recruitment had been of individuals carrying just 0 or 0 plus 1 CYP2D6 active genes, due to the lower CV(w). This suggests that there may be a role for pharmacogenetics in the design of bioequivalence studies to reduce sample size and costs, thus introducing a new paradigm for the biopharmaceutical evaluation of drug products. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|