title: Intuitive pharmacogenetics: spontaneous risperidone dosage is related to CYP2D6, CYP3A5 and ABCB1 genotypes.
abstract: The aim of this study is to evaluate whether the quantitative prescription of risperidone (dosage) is related to the patient's metabolic status. Metabolic status was defined in terms of the most relevant polymorphisms of CYP2D6 (*3, *4, *5, *6 and *1xN), CYP3A5 (*3A) and ABCB1 (G2677T) determined a posteriori and blinded to the clinicians. This prospective and observational study includes a cohort of 151 Caucasian psychiatric patients treated with risperidone. Significant differences (Kruskal-Wallis test p=0.01) among the doses administered were observed to correlate (Spearman's r=1, p=0.02) with the different CYP2D6 groups. Poor metabolizers received the lowest doses and ultra rapid metabolizers the highest. No significant correlations were observed with regard to CYP3A5 and ABCB1. We find that, despite not knowing patients' metabolic status, clinicians modify risperidone dosage in order to obtain the best therapeutic option.
authors.affiliation: Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Mas
authors.forename: P
authors.initials: P
authors.lastname: Gassò
authors.forename: S
authors.initials: S
authors.lastname: Alvarez
authors.forename: E
authors.initials: E
authors.lastname: Parellada
authors.forename: M
authors.initials: M
authors.lastname: Bernardo
authors.forename: A
authors.initials: A
authors.lastname: Lafuente
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D054796:Drug Dosage Calculations; D016903:Drug Monitoring; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D019545:Intuition; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D018967:Risperidone / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D012559:Schizophrenia / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics / Q000378:metabolism; D013030:Spain / Q000453:epidemiology; D016896:Treatment Outcome; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014150:Antipsychotic Agents; C510164:CYP3A5 protein, human; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D018967:Risperidone