Table_1_Quantifying the Impact of Phenoconversion on Medications With Actionable Pharmacogenomic Guideline Recommendations in an Acute Aged Persons Mental Health Setting.DOCX

Introduction: 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.
Aim: 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).
Methods: Acute aged persons mental health patients (N = 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.
Results: 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.
Discussion: 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.

引言：多重用药与显著影响药物反应的遗传变异（药物基因组学，pharmacogenomics, PGx）是药品不良反应的两大公认风险因素。当存在可引发细胞色素P450（cytochrome P450）酶表型转换的合并用药时，药物基因组学结果的解读会变得复杂。
研究目的：量化急性老年精神疾病患者队列中的表型转换发生情况，并评估其对携带可操作药物基因组学指南推荐（actionable PGx guideline recommendations, APRs）的药物标注的影响。
研究方法：选取入院及出院时均具备药物基因组学与用药数据的急性老年精神疾病患者共137例（N=137），以分析细胞色素P450 2D6（CYP2D6）、细胞色素P450 2C19（CYP2C19）及细胞色素P450 2C9（CYP2C9）的表型转换发生频率。随后评估表型转换对携带APRs的药物标注的预期影响。
研究结果：表型转换后，细胞色素P450 2D6中间代谢型（intermediate metabolisers, IMs）患者在入院及出院时的预测频率分别升高11.7%与16.1%。同理，细胞色素P450 2C19 IMs患者的入院及出院预测频率分别升高13.1%与11.7%。入院时，共开具120剂次携带APRs的药物，其中42%（50剂次）在表型转换前即具备APRs，表型转换后该数值升至60剂次（占比50%）。出院时，共开具122剂次携带APRs的药物，其中39%（48剂次）在表型转换前即具备APRs，表型转换后该数值升至57剂次（占比47%）。
讨论：老年精神疾病患者常被开具携带APRs的药物，但解读此类推荐时必须考虑表型转换的影响。建议采用处方医师与临床药师协作的诊疗模式，以应对表型转换问题，确保药物基因组学的潜在获益得以最大化。