The predictive value of ABCB1, ABCG2, CYP3A4/5 and CYP2D6 polymorphisms for risperidone and aripiprazole plasma concentrations and the occurrence of adverse drug reactions

• Published in: The pharmacogenomics journal Vol. 18; no. 3; pp. 422 - 430
• Main Authors: Rafaniello, C, Sessa, M, Bernardi, F F, Pozzi, M, Cheli, S, Cattaneo, D, Baldelli, S, Molteni, M, Bernardini, R, Rossi, F, Clementi, E, Bravaccio, C, Radice, S, Capuano, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22-05-2018; Nature Publishing Group
• Subjects: 631/208/1516/1510; 692/700/478; ABCG2 gene; Adverse drug reactions; Antipsychotics; Aripiprazole; Biomedical and Life Sciences; Biomedicine; Childhood mental disorders; Comparative analysis; CYP2D6 protein; Cytochrome P-450; Cytochrome P450; Dosage and administration; Drug metabolism; Drug therapy; Gene Expression; Genetic aspects; Genetic polymorphisms; Genotype & phenotype; Genotypes; Health aspects; Human Genetics; Metabolism; Multivariate analysis; Nutrition disorders; Oncology; original-article; Pediatrics; Pharmacogenomics; Pharmacological research; Pharmacotherapy; Physiological aspects; Psychopharmacology; Risperidone; Side effects; Statistical analysis; Europe
• ISSN: 1470-269X; 1473-1150
• DOI: 10.1038/tpj.2017.38

We investigated in ninety Caucasian pediatric patients the impact of the main polymorphisms occurring in
CYP3A
,
CYP2D6
,
ABCB1
and
ABCG2
genes on second-generation antipsychotics plasma concentrations, and their association with the occurrence of adverse drug reactions. Patients with the CA/AA
ABCG2
genotype had a statistically significant lower risperidone plasma concentration/dose ratio (Ct/ds) (
P
-value: 0.007) and an higher estimated marginal probability of developing metabolism and nutrition disorders as compared to the
ABCG2
c.421 non-CA/AA genotypes (
P
-value: 0.008). Multivariate analysis revealed that the
ABCG2
c.421 CA/AA genotype was found associated to a higher hazard (
P
-value: 0.004) of developing adverse drug reactions classified as metabolism and nutrition disorders. The
ABCB1
2677TT/3435TT genotype had a statistically significant lower aripiprazole Ct/ds if compared with patients with others
ABCB1
genotypes (
P
-value: 0.026). Information obtained on
ABCB1
and
ABCG2
gene variants may result useful to tailor treatments with these drugs in Caucasian pediatric patients.