Aim: To elucidate the relationship between CYP2D6 genotype and risperidone pharmacokinetics and extrapyramidal symptoms we propose the APSEP pharmacogenetic clinical trial.
Materials & methods: Twenty-five healthy subjects were included in this randomized, placebo-controlled, single dose (risperidone 2.5 mg) crossover and double-blind clinical trial. Subjects were selected according to their CYP2D6 genotype and classified as: poor metabolizers (n = 8), extensive metabolizers (n = 10) and ultrarapid metabolizers (n = 7).
Results & conclusion: Our study demonstrates that CYP2D6 predicted 65% of the risperidone metabolism variability. Moreover, its ability to predict actigraphy records is similar to the predictive power of pharmacokinetic parameters (24%). Our results also highlight the need for the development of pharmacogenetic predictors that take into account the complexity of pharmacokinetic and pharmacodynamic relationships.