不同细胞色素P4502C19基因型患者伏立康唑稳态血药谷浓度的系统评价

Voriconazole steady- state plasma trough concentrations in patients with cytochrome 2C19 polymorphism: A systematic review

目的评价细胞色素P450 2C19(CYP2C19)慢代谢型患者(PMs)、杂合子快代谢型患者(HEMs)、纯合子快代谢型患者(EMs)的伏立康唑稳态血药谷浓度。方法系统检索建库至2015年3月Pub Med、Em Base、Cochrane Library、Clinical Trials.gov、中国知网(CNKI)、万方和中国生物医学文献(CBM)数据库。纳入所有报告PMs、HEMs或EMs伏立康唑稳态血药谷浓度的临床试验或研究,排除使用非说明书推荐方案给药和人群为健康受试者的研究。用随机效应模型对各研究结果进行单臂荟萃分析,分别计算PMs、HEMs和EMs患者的稳态血药谷浓度。结果纳入5篇研究,包括39名PMs、143名HEMs和170名EMs。PMs、HEMs和EMs的稳态血药浓度分别为4.21,2.47,2.00μg·m L-1。结论没有必要常规测定患者CYP2C19基因型以调整伏立康唑初始给药方案。

Objective To estimate voriconazole steady- state plasma trough concentrations in cytochrome 2C19 （CYP2C19） poor metabolizers （PMs）, heterozygous extensive metabolizers （HEMs） and extensive me- tabolizers （EMs） when using standard dosing regimen. Methods PubMed, EmBase, the Cochrane Library, Clinicahriasl. gov and three Chinese databases （CNKI, CBM, and WanFang） were searched through March 2015. Clinical trials and observational studies reporting voricon- azole steady - state plasma trough concentrations of PMs, HEMs, or EMs were included. Studies with healthy subjects or patients using non - standard voriconazole dosing regimen were excluded. Single -arm meta - analysis was performed using the random effect model. Estimated steady - state plasma trough concentrations with 95% confidence intervals （95% CIs） were calculated for PMs, HEMs and EMs respectively. Results Five observational studies were included in the single -arm meta analysis. The sample sizes of PMs, HEMs and EMs were 39, 143 and 170 respectively. Calculated vorlconazole steady - state plasma trough concentrations for PMs, HEMs and EMs were 4.21, 2.47, 2.00ug ·mL-1 respectively. Conclusion It is unnecessary to adjust initial voriconazole dosing regimen by routine CYP2C19 genotype test.