CYP2C19-guided voriconazole dosing reduces pharmacokinetic variability, but many patients remain subtherapeutic. The aim of this study was to evaluate the effect of candidate genes and a novel CYP2C haplotype on voriconazole trough concentrations in patients receiving CYP2C19-guided dosing. This is a retrospective candidate gene study in allogeneic hematopoietic cell transplant (HCT) patients receiving CYP2C19-guided voriconazole dosing. Patients were genotyped for ABCB1, ABCG2, CYP2C9, CYP3A4, CYP3A5, and the CYP2C haplotype. Of 185 patients, 36% were subtherapeutic (of which 79% were normal or intermediate metabolizers). In all patients, CYP2C19 (p < 0.001), age (p = 0.018), and letermovir use (p = 0.001) were associated with voriconazole concentrations. In the subset receiving 200 mg daily (non-RM/UMs), CYP2C19 (p = 0.004) and ABCG2 (p = 0.015) were associated with voriconazole concentrations; CYP2C19 (p = 0.028) and letermovir use (p = 0.001) were associated with subtherapeutic status. CYP2C19 phenotype and letermovir use were significantly associated with subtherapeutic voriconazole concentrations and may be used to improve voriconazole precision dosing, while further research is needed to clarify the role of ABCG2 in voriconazole dosing.

CYP2C19指导的伏立康唑给药可降低药代动力学变异性，但许多患者仍处于亚治疗状态。本研究的目的是评估候选基因和新型CYP2C单倍型对接受CYP2C19指导给药的患者伏立康唑谷浓度的影响。这是一项针对接受CYP2C19指导伏立康唑给药的同种异体造血细胞移植 (HCT) 患者的回顾性候选基因研究。对患者进行了ABCB1、ABCG2、CYP2C9、CYP3A4、CYP3A5和CYP2C单倍型的基因分型。在 185 名患者中，36% 处于亚治疗状态（其中 79% 为正常或中间代谢者）。在所有患者中，CYP2C19（p  < 0.001）、年龄（p  = 0.018）和莱特莫韦的使用（p  = 0.001）与伏立康唑浓度相关。在每天接受 200 mg 剂量（非 RM/UM）的子集中，CYP2C19 ( p  = 0.004) 和ABCG2 ( p  = 0.015) 与伏立康唑浓度相关；CYP2C19 ( p  = 0.028) 和莱特莫韦的使用 ( p  = 0.001) 与亚治疗状态相关。CYP2C19表型和莱特莫韦的使用与亚治疗伏立康唑浓度显着相关，可用于提高伏立康唑的精确剂量，而需要进一步研究来阐明ABCG2在伏立康唑剂量中的作用。