The influence of CYP2C19 polymorphisms on voriconazole trough concentrations: Systematic review and meta‐analysis

CYP2C19型 伏立康唑 荟萃分析 槽浓度 医学 胃肠病学 槽水位 药理学 内科学 药代动力学 抗真菌 皮肤病科 细胞色素P450 新陈代谢 移植 他克莫司
作者
Ying Zhang,Kelu Hou,Fang Liu,Xingxian Luo,Songjie He,Lei Hu,Yang Chen,Lin Huang,Yufei Feng
出处
期刊:Mycoses [Wiley]
卷期号:64 (8): 860-873 被引量:21
标识
DOI:10.1111/myc.13293
摘要

Abstract Background Voriconazole primary metabolism is catalysed by CYP2C19. A large variability of trough concentrations in patients with invasive fungal infection treated with voriconazole has been observed in clinical practice. It remains controversial whether the CYP2C19 polymorphisms are responsible for voriconazole metabolism in the individual variation. Objectives The primary aim of this study was to assess the effect of CYP2C19 polymorphisms on voriconazole trough concentrations. Methods Following a systematic literature review, we performed a meta‐analysis for mean differences (MD) of voriconazole trough concentrations (C min ), voriconazole dosage adjusted trough concentrations (C min /D) and for risk ratio (RR) of the proportion of patients in the target therapeutic range between pairwise comparisons of CYP2C19 phenotypes. Results Compared with normal metabolisers (NMs), intermediate metabolisers (IMs) (MD: 0.82, 95% CI: 0.57 to 1.07, I 2 = 44%, p < .00001) or poor metabolisers (PMs) (MD: 1.59, 95% CI: 1.14 to 2.05, I 2 = 46%, p < .00001) had significantly higher voriconazole C min (μg·ml −1 ), while rapid metabolisers (RMs) had significantly lower voriconazole C min (MD: −0,87, 95% CI: −1.35 to −0.38, I 2 = 0%, p = .0004). In addition, IMs had significantly lower C min than PMs (MD: −0.59, 95% CI: −0.97 to −0.20, I 2 = 22%, p = .003). Similarly, the C min /D (μg·kg·ml −1 ·mg −1 ) was significantly higher in IMs (MD: 0.13, 95% CI: 0.05 to 0.22, I 2 = 0%, p = .002) and PMs (MD: 0.20, 95% CI: 0.07 to 0.34, I 2 = 0%, p = .003) than that in NMs, and also, IMs had significantly lower C min /D than PMs (MD: −0.11, 95% CI: −0.14 to −0.08, I 2 = 0%, p < .00001). Furthermore, PMs had a significantly higher proportion of the target therapeutic range than NMs (RR: 1.34, 95% CI: 1.09 to 1.64, I 2 = 50%, p = .005). Conclusions Compared to NMs, IMs and PMs had higher voriconazole trough concentrations, especially in Asians, while RMs had lower voriconazole trough concentrations. In addition, PMs had a higher proportion of the target therapeutic range than NMs, especially in Asians. CYP2C19 genotyping is expected to be used to preemptively guide the individualisation of voriconazole in clinical practice.
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