Therapeutic Drug Monitoring and Genotypic Screening in the Clinical Use of Voriconazole.
Therapeutic Drug Monitoring and Genotypic Screening in the Clinical Use of Voriconazole.
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DOI：
10.1007/s12281-015-0219-0
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发表时间：
2015-06
影响因子：
1.4
通讯作者：
Penzak SR
中科院分区：
文献类型：
--
作者：
Moriyama B;Kadri S;Henning SA;Danner RL;Walsh TJ;Penzak SR
伏立康唑是一种抗真菌三唑类药物，是治疗侵袭性曲霉病的一线药物。它通过CYP2C19、CYP2C9和CYP3A4代谢，并显示出血清浓度的广泛患者间变异性。CYP2C19的多态性导致伏立康唑药代动力学的变异性。在这里，研究使用伏立康唑治疗药物监测（TDM）和CYP2C19基因分型在伏立康唑给药中的作用的证据。大多数探索伏立康唑TDM对疗效和安全性影响的研究发现TDM有益。然而，这些研究大多是观察性的，只有一项是随机对照试验。目前尚没有大量的TDM多中心随机对照试验来支持明确的指南。在健康志愿者中，CYP2C19基因型与伏立康唑药代动力学之间存在显著相关性，但这种相关性在实际患者中明显不明显。虽然CYP2C19基因型数据可以解释伏立康唑血清浓度的变异性，但它们本身不足以指导初始给药。在个体患者治疗中及时获得CYP2C19基因型数据也仍然具有挑战性。在将伏立康唑给药的CYP2C19基因分型纳入常规临床护理之前，需要进行额外的研究。
Voriconazole is an antifungal triazole that is the first line agent for treatment of invasive aspergillosis. It is metabolized by CYP2C19, CYP2C9, and CYP3A4 and demonstrates wide interpatient variability in serum concentrations. Polymorphisms in CYP2C19 contribute to variability in voriconazole pharmacokinetics. Here, evidence is examined for the use of voriconazole therapeutic drug monitoring (TDM) and the role of CYP2C19 genotyping in voriconazole dosing. The majority of studies exploring the impact of voriconazole TDM on efficacy and safety have found TDM to be beneficial. However, most of these studies are observational, with only one being a randomized controlled trial. High-volume multicenter randomized controlled trials of TDM are currently not available to support definitive guidelines. There is a significant relationship in healthy volunteers between CYP2C19 genotype and voriconazole pharmacokinetics, but this association is markedly less visible in actual patients. While CYP2C19 genotype data may explain variability of voriconazole serum levels, they alone are not sufficient to guide initial dosing. The timeliness of availability of CYP2C19 genotype data in treatment of individual patients also remains challenging. Additional studies are needed before implementation of CYP2C19 genotyping for voriconazole dosing into routine clinical care.