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Relationship between CYP2D6 genotype and haloperidol pharmacokinetics and extrapyramidal symptoms in healthy
Patricia Gassó1, Katerina Papagianni, Sergi Mas
1Department of Anatomic Pathology, Pharmacology & Microbiology, School of Medicine, University of Barcelona, IDIBAPS, Casanova 143, E-08036 Barcelona, Spain.
Aim:
This study aimed to elucidate the relationship between CYP2D6 genotype and haloperidol pharmacokinetics and induced extrapyramidal symptoms (EPSs).
Materials & Methods:
Twenty five healthy subjects were included in this randomized, placebo-controlled, single-dose (5 mg) crossover and double-blind clinical trial, selected according to their CYP2D6 genotype and classified as poor metabolizers (n = 8), extensive metabolizers (n = 10) and ultrarapid metabolizers (n = 7).
Results & Conclusion:
We confirm that CYP2D6 genotype partially determines haloperidol metabolism and the rate of EPSs measured as wakefulness activity by actigraphy. The best predictor of wakefulness activity was the model including haloperidol area under the plasma concentration-time curve, sex and tranquilization, which explained 48.3% of the total variance. However, other markers need to be identified in order to explain the observed variability of haloperidol response and to develop pharmacogenetic predictors of haloperidol-induced EPSs.
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