title: Polymorphisms in CYP2D6 have a greater effect on variability of risperidone pharmacokinetics than gender.
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.
authors: Service of Clinical Pharmacology, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain.
authors: Teresa
authors: T
authors: Cabaleiro
authors: Dolores
authors: D
authors: Ochoa
authors: Manuel
authors: M
authors: Román
authors: Isabel
authors: I
authors: Moreno
authors: Rosario
authors: R
authors: López-Rodríguez
authors: Jesús
authors: J
authors: Novalbos
authors: Francisco
authors: F
authors: Abad-Santos
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D018967:Risperidone / Q000493:pharmacokinetics*; D012737:Sex Factors; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6; D018967:Risperidone