CYP2C19 drug-drug and drug-gene interactions in ED patients

被引:9
作者
Flaten, Hanna K. [1 ]
Kim, Howard S. [2 ]
Campbell, Jenny [1 ]
Hamilton, Lisa [3 ]
Monte, Andrew A. [1 ,2 ,3 ,4 ,5 ]
机构
[1] Univ Colorado, Dept Emergency Med, 12401 E 17th Ave, Aurora, CO 80045 USA
[2] Denver Hlth Residency Emergency Med, 770 Bannock St, Denver, CO 80204 USA
[3] Univ Colorado, Sch Med, 12401 E 17th Ave, Aurora, CO 80045 USA
[4] Skaggs Sch Pharm & Pharmaceut Sci, 12401 E 17th Ave, Aurora, CO 80045 USA
[5] Rocky Mt Poison & Drug Ctr, 990 Bannock St, Denver, CO 80204 USA
基金
美国国家卫生研究院;
关键词
S-MEPHENYTOIN; HYPERSENSITIVITY REACTIONS; CAUCASIAN POPULATIONS; PHARMACOGENETICS; POLYMORPHISM; 2C19; METABOLISM; GENOTYPE; ISOFORMS; METAANALYSIS;
D O I
10.1016/j.ajem.2015.10.055
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Background: CYP450 polymorphisms result in variable rates of drug metabolism. CYP drug-drug interactions can contribute to altered drug effectiveness and safety. Study objectives: The primary objective was to determine the percentage of emergency department (ED) patients with cytochrome 2C19 (CYP2C19) drug-drug interactions. The secondary objective was to determine the prevalence of CYP2C19 polymorphisms in a US ED population. Methods: We conducted a prospective observational study in an urban academic ED with 72,000 annual visits. Drug ingestion histories for the 48 hours preceding ED visit were obtained; each drug was coded as CYP2C19 substrate, inhibitor, inducer, or not CYP2C19 dependent. Ten percent of patients were randomized to undergo CYP2C19 genotyping using the Roche Amplichip. Results: A total of 502 patients were included; 61% were female, 65% were white, and median age was 39 years (interquartile range, 22-53). One hundred thirty-one (26.1%) patients had taken at least 1 CYP2C19-dependent home drug. Eighteen (13.7%) patients who were already taking a CYP2C19-dependent drug were given or prescribed a CYP2C19-dependent drug while in the ED. Among the 53 patients genotyped, 52 (98%) were extensive metabolizers and 1 was a poor metabolizer. Conclusions: In a population of ED patients, more than a quarter had taken a CYP2C19-dependent drug in the preceding 48 hours, but few were given or prescribed another CYP2C19-dependent drug in the ED. On genotyping analysis, CYP2C19 polymorphisms were uncommon in our cohort. We conclude that changing prescribing practice due to CYP2C19 drug-drug interaction or genotype is unlikely to be useful in most US ED populations. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:245 / 249
页数:5
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