期刊
PHARMACOTHERAPY
卷 42, 期 6, 页码 453-459出版社
WILEY
DOI: 10.1002/phar.2684
关键词
adrenergic; alpha-2; child; dexmedetomidine; pharmacogenetics; receptor
This study aimed to determine the association between ADRA2A genotype and dexmedetomidine dose in children. The results showed that the relationship between ADRA2A genotype and dexmedetomidine response is not clear in children, highlighting the need for pediatric studies to validate PGx findings in adults.
Study Objective Dexmedetomidine is titrated to achieve sedation in the pediatric and cardiovascular intensive care units (PICU and CVICU). In adults, dexmedetomidine response has been associated with an ADRA2A polymorphism (rs1800544); CC genotype is associated with an increased sedative response compared with GC and GG. To date, this has not been studied in children. Design We conducted a pilot study to determine whether ADRA2A genotype is associated with dexmedetomidine dose in children. Measurements and Main Results Forty intubated PICU or CVICU patients who received dexmedetomidine as a continuous infusion for at least 2 days were genotyped for ADRA2A with a custom-designed TaqMan (R) Assay. Ten (25%) subjects were wildtype (GG), 15 (37.5%) were heterozygous (GC), and 15 (37.5%) were homozygous (CC) variant. The maximum dexmedetomidine doses (mCg/kg/h) were not different between genotype groups CC (1, 0.3-1.2), GC (1, 0.3-1.3), and GG (0.8, 0.3-1.2), (p = 0.37); neither were mean dexmedetomidine doses for these respective genotype groups 0.68 (0.24-1.07), 0.72 (0.22-0.98), 0.58 (0.3-0.94), (p = 0.67). Conclusions These findings did not confirm the results from adult studies where ADRA2A polymorphisms correlate with dexmedetomidine response, therefore highlighting the need for pediatric studies to validate PGx findings in adults prior to implementation in pediatrics.
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