Effects of chromosomal variations on pharmacokinetic activity of zolpidem in healthy volunteers: an array-based comparative genomic hybridization study.
Zolpidem has been known as a very safe and effective hypnotic drug used to treat a variety of patients with insomnia. Even though the same dose of the medicine is administered to each patient, the blood level of zolpidem and the time required to obtain peak concentration are not consistent among different people. We evaluated the relationship between the peak concentrations of zolpidem and chromosomal imbalances using a high-resolution genome-wide array-based comparative genomic hybridization (CGH) in 16 healthy volunteers in order to detect the genetic factors underlying the variations. The present study showed that chromosomal losses were detected in the 4q35.2, 9p13.1 and 9p12 regions, and those gains were indicated in the 2p14, 11q13.4 and 15q11.2 regions. The abnormal regions were confirmed by fluorescence in situ hybridization (FISH) and real-time PCR. It is suggested that array-CGH analysis may be used as a measure for pharmacogenomic applications in the patients with insomnia and for further exploration of candidate genomic regions implicated in sleep disturbances.
Moon
Ho-Jin
HJ
Department of Pharmacology, College of Medicine, and Department of Psychiatry, Our Lady of Mercy Hospital, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
Choi
Jin Soo
JS
Park
E-Jin
EJ
Kang
Chin-Yang
CY
Jeon
Yang-Whan
YW
Lee
Kweon-Haeng
KH
Rha
Hyoung Kyun
HK
Han
Sang-Ick
SI
D000328:Adult; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008657:Metabolic Clearance Rate; D011725:Pyridines / Q000097:blood* / Q000493:pharmacokinetics*; D012016:Reference Values; D000077334:Zolpidem
D011725:Pyridines; D000077334:Zolpidem