Polymorphisms in CYP2D6 have a Greater Effect on Variability of Risperidone Pharmacokinetics than Gender |
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| Authors: | Teresa Cabaleiro Dolores Ochoa Manuel Román Isabel Moreno Rosario López‐Rodríguez Jesús Novalbos Francisco Abad‐Santos |
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| Affiliation: | 1. Service of Clinical Pharmacology, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain;2. Liver Unit, Gastroenterology Service, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain;3. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain |
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| Abstract: | Within‐subject coefficient of variation (CVw) plays a decisive role in the determination of sample size in bioequivalence clinical trials. Highly variable drugs may require the participation of a large number of subjects. The aim of this study was to investigate whether gender and polymorphisms in CYP2D6 affect the CVw of risperidone. Two single‐dose, two‐period crossover studies of risperidone (n = 70) were reanalysed to calculate CVw for AUCt and Cmax. Subjects were classified into four different CYP2D6 phenotype groups [poor metabolizers (PM), intermediate metabolizers (IM), extensive metabolizers (EM) and ultrarapid metabolizers (UM)]. The effect of gender was evaluated in EM and IM. CVw was lower in PM (13.3% for AUCt and 10.9% for Cmax) and UM (17.4% and 8.7%) than in EM (28.7% and 34.7%) and IM (33.2% and 27.3%). Variability was slightly lower in women (27.9% for AUCt and 25.7% for Cmax) than in men (33.3% and 37.2%, respectively). Genetic polymorphisms affect within‐subject variability more than gender and could considerably affect sample size calculation. Therefore, subjects participating in bioequivalence trials should be genotyped. |
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