Mostafa Sam, Polasek Thomas M, Sheffield Leslie J, Huppert David, Kirkpatrick Carl M J
Centre for Medicine Use and Safety, Monash University, Parkville, VIC, Australia.
MyDNA Life, Australia Limited, South Yarra, VIC, Australia.
Front Psychiatry. 2021 Aug 19;12:724170. doi: 10.3389/fpsyt.2021.724170. eCollection 2021.
Polypharmacy and genetic variants that strongly influence medication response (pharmacogenomics, PGx) are two well-described risk factors for adverse drug reactions. Complexities arise in interpreting PGx results in the presence of co-administered medications that can cause cytochrome P450 enzyme phenoconversion. To quantify phenoconversion in a cohort of acute aged persons mental health patients and evaluate its impact on the reporting of medications with actionable PGx guideline recommendations (APRs). Acute aged persons mental health patients ( = 137) with PGx and medication data at admission and discharge were selected to describe phenoconversion frequencies for CYP2D6, CYP2C19 and CYP2C9 enzymes. The expected impact of phenoconversion was then assessed on the reporting of medications with APRs. Post-phenoconversion, the predicted frequency at admission and discharge increased for CYP2D6 intermediate metabolisers (IMs) by 11.7 and 16.1%, respectively. Similarly, for CYP2C19 IMs, the predicted frequency at admission and discharge increased by 13.1 and 11.7%, respectively. Nineteen medications with APRs were prescribed 120 times at admission, of which 50 (42%) had APRs pre-phenoconversion, increasing to 60 prescriptions (50%) post-phenoconversion. At discharge, 18 medications with APRs were prescribed 122 times, of which 48 (39%) had APRs pre-phenoconversion, increasing to 57 prescriptions (47%) post-phenoconversion. Aged persons mental health patients are commonly prescribed medications with APRs, but interpretation of these recommendations must consider the effects of phenoconversion. Adopting a collaborative care model between prescribers and clinical pharmacists should be considered to address phenoconversion and ensure the potential benefits of PGx are maximised.
多重用药以及强烈影响药物反应的基因变异（药物基因组学，PGx）是两个已被充分描述的药物不良反应风险因素。在同时使用可导致细胞色素P450酶表型转换的药物时，解读PGx结果会出现复杂性。为了量化一组急性老年心理健康患者中的表型转换情况，并评估其对具有可操作PGx指南建议（APRs）的药物报告的影响。选择了入院和出院时具有PGx和用药数据的急性老年心理健康患者（n = 137）来描述CYP2D6、CYP2C19和CYP2C9酶的表型转换频率。然后评估表型转换对具有APRs的药物报告的预期影响。表型转换后，CYP2D6中间代谢者（IMs）入院和出院时的预测频率分别增加了11.7%和16.1%。同样，对于CYP2C19 IMs，入院和出院时的预测频率分别增加了13.1%和11.7%。19种具有APRs的药物在入院时被处方120次，其中50次（42%）在表型转换前具有APRs，表型转换后增加到60次处方（50%）。出院时，18种具有APRs的药物被处方122次，其中48次（39%）在表型转换前具有APRs，表型转换后增加到57次处方（47%）。老年心理健康患者通常会被处方具有APRs的药物，但对这些建议的解读必须考虑表型转换的影响。应考虑在开处方者和临床药剂师之间采用协作护理模式，以解决表型转换问题，并确保PGx的潜在益处得到最大化。
