Zhang Jingru, Liu Yiwei, Nie Xiaolu, Yu Yuncui, Gu Jian, Zhao Libo
Clinical Research Center, Beijing Children's Hospital, Capital Medical University, Beijing, China,
Department of Pharmacy Administration and Clinical Pharmacy, Peking University School of Pharmaceutical Sciences, Beijing, China.
Infect Drug Resist. 2018 Aug 22;11:1283-1297. doi: 10.2147/IDR.S170706. eCollection 2018.
The optimum trough concentration of itraconazole for clinical response and safty is controversial. The objective of this systematic review and meta-analysis was to determine the optimum trough concentration of itraconazole and evaluate its relationship with efficacy and safety.
We searched PubMed, EMBASE, Web of Science, the Cochrane Library, Clinical-Trials.gov, and three Chinese literature databases (CNKI, WanFang, and CBM). We included observational studies that compared clinical outcomes below or above the trough concentration cut-off value which we set as 0.25, 0.5, and 1.0 mg/L. The efficacy outcomes were rate of successful treatment, rate of prophylaxis failure and invasive fungal infection (IFI)-related mortality. The safety outcomes included incidents of hepatotoxicity and other adverse events.
The study included a total of 29 studies involving 2,346 patients. Our meta-analysis showed that compared with itraconazole trough concentrations (C) of ≥0.25 mg/L, levels of <0.25 mg/L significantly increased the incidence of IFI for prophylaxis (RR =3.279, 95% confidence interval [CI] 1.73-6.206). Moreover, the success rate of treatment decreased significantly at a cut-off level of 0.5 mg/L (RR =0.396, 95% CI 0.176-0.889). An itraconazole trough level of 1.0 mg/L was associated with hepatotoxicity and other adverse events in a review of many studies.
An itraconazole trough concentration of 0.25 mg/L should be considered as the lower threshold for prophylaxis, and a target concentration of 0.5 mg/L should be the lower limit for effective treatment. A trough level of 1.0 mg/L is associated with increased hepatotoxicity and other adverse events (using High Performance Liquid Chromatography [HPLC]).
伊曲康唑达到临床疗效和安全性的最佳谷浓度存在争议。本系统评价和荟萃分析的目的是确定伊曲康唑的最佳谷浓度，并评估其与疗效和安全性的关系。
我们检索了PubMed、EMBASE、Web of Science、Cochrane图书馆、Clinical-Trials.gov以及三个中文文献数据库（中国知网、万方和中国生物医学文献数据库）。我们纳入了观察性研究，这些研究比较了谷浓度临界值（我们设定为0.25、0.5和1.0mg/L）以下或以上的临床结局。疗效结局包括成功治疗率、预防失败率和侵袭性真菌感染（IFI）相关死亡率。安全性结局包括肝毒性事件和其他不良事件。
该研究共纳入29项研究，涉及2346例患者。我们的荟萃分析表明，与伊曲康唑谷浓度（C）≥0.25mg/L相比，<0.25mg/L显著增加了预防IFI的发生率（风险比[RR]=3.279，95%置信区间[CI]1.73-6.206）。此外，在临界值为0.5mg/L时，治疗成功率显著降低（RR=0.396，95%CI 0.176-0.889）。在对多项研究的综述中，伊曲康唑谷浓度为1.0mg/L与肝毒性和其他不良事件相关。
应将伊曲康唑谷浓度0.25mg/L视为预防的下限阈值，而目标浓度0.5mg/L应作为有效治疗的下限。谷浓度1.0mg/L与肝毒性和其他不良事件增加相关（使用高效液相色谱法[HPLC]）。
