Effects of DRD2 and CYP2D6 genotypes on delta EEG power response to aripiprazole in healthy male volunteers: a preliminary study.
The aim of the present study was to evaluate the effects of polymorphisms in dopamine D2 receptor (DRD2) and cytochrome P450 (CYP) 2D6 genes on delta EEG power response to aripiprazole in healthy male volunteers. Seventeen volunteers were recruited according to the DRD2 Taq1A genotype, and separated into the following groups: homozygous wild-type (A2/A2, n = 7), heterozygous (A2/A1, n = 5) and homozygous variant-type (A1/A1, n = 5) groups. After enrollment in this study, they were genotyped for CYP2D6. The volunteers received single 10 mg oral doses of aripiprazole, in accordance with an open-label parallel group study design. Plasma levels of aripiprazole and its metabolite were determined and EEGs were obtained simultaneously. The pharmacodynamic parameter was absolute delta power in the Cz channel. The changes of delta power were not different according to DRD2 Taq1A genotypes. As to the CYP2D6 allele, the subjects had the following CYP2D6 genotypes: *10/*10 (n = 4), *1/*10 (n = 5), *1/*5 (n = 2), *1/*1 (n = 3), *2/*41 (n = 1), *2/*2 (n = 1), *2N/*10 (n = 1). Subjects exhibiting the *1/*5 and *1/*10 genotypes showed a trend toward high area under the plasma aripiprazole concentration-time curve (AUC), which was linearly related to area under the EEG response-time curve (AUEC). Our results demonstrate a need for further evaluation of the CYP2D6 genotypic effect on the pharmacodynamics of aripiprazole.
Kim
Euitae
E
Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea.
Yu
Kyung-Sang
KS
Cho
Joo-Youn
JY
Shin
Yong-Wook
YW
Yoo
So Young
SY
Kim
Young Youn
YY
Jang
In-Jin
IJ
Shin
Sang-Goo
SG
Kwon
Jun Soo
JS
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology; D019540:Area Under Curve; D000068180:Aripiprazole; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004569:Electroencephalography / Q000187:drug effects; D005838:Genotype; D006207:Half-Life; D006801:Humans; D008297:Male; D010641:Phenotype; D010879:Piperazines / Q000494:pharmacology; D011110:Polymorphism, Genetic; D015363:Quinolones / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014150:Antipsychotic Agents; C504128:OPC-14857; D010879:Piperazines; D015363:Quinolones; D017448:Receptors, Dopamine D2; D000068180:Aripiprazole; D019389:Cytochrome P-450 CYP2D6