Jin Haiying, Wang Tiansheng, Falcione Bonnie A, Olsen Keith M, Chen Ken, Tang Huilin, Hui John, Zhai Suodi
Department of Pharmacy, Peking University Third Hospital, Beijing, China Department of Pharmacy, The Affiliated Hospital of Medical College, Ningbo University, Ningbo, Zhejiang, China.
Department of Pharmacy, Peking University Third Hospital, Beijing, China Department of Pharmacy Administration and Clinical Pharmacy, Peking University School of Pharmaceutical Sciences, Beijing, China
J Antimicrob Chemother. 2016 Jul;71(7):1772-85. doi: 10.1093/jac/dkw045. Epub 2016 Mar 10.
The optimum trough concentration of voriconazole for clinical response and safety is controversial. The objective of this review was to determine the optimum trough concentration of voriconazole and evaluate its relationship with efficacy and safety.
MEDLINE, EMBASE, ClinicalTrials.gov, the Cochrane Library and three Chinese literature databases were searched. Observational studies that compared clinical outcomes below and above the trough concentration cut-off value were included. We set the trough concentration cut-off value for efficacy as 0.5, 1.0, 1.5, 2.0 and 3.0 mg/L and for safety as 3.0, 4.0, 5.0, 5.5 and 6.0 mg/L. The efficacy outcomes were invasive fungal infection-related mortality, all-cause mortality, rate of successful treatment and rate of prophylaxis failure. The safety outcomes included incidents of hepatotoxicity, neurotoxicity and visual disorders.
A total of 21 studies involving 1158 patients were included. Compared with voriconazole trough concentrations of >0.5 mg/L, levels of <0.5 mg/L significantly decreased the rate of treatment success (risk ratio = 0.46, 95% CI 0.29-0.74). The incidence of hepatotoxicity was significantly increased with trough concentrations >3.0, >4.0, >5.5 and >6.0 mg/L. The incidence of neurotoxicity was significantly increased with trough concentrations >4.0 and >5.5 mg/L.
A voriconazole level of 0.5 mg/L should be considered the lower threshold associated with efficacy. A trough concentration >3.0 mg/L is associated with increased hepatotoxicity, particularly for the Asian population, and >4.0 mg/L is associated with increased neurotoxicity.
伏立康唑达到临床疗效和安全性的最佳谷浓度存在争议。本综述的目的是确定伏立康唑的最佳谷浓度，并评估其与疗效和安全性的关系。
检索了MEDLINE、EMBASE、ClinicalTrials.gov、Cochrane图书馆和三个中文文献数据库。纳入比较谷浓度临界值上下的临床结局的观察性研究。我们将疗效的谷浓度临界值设定为0.5、1.0、1.5、2.0和3.0mg/L，安全性的谷浓度临界值设定为3.0、4.0、5.0、5.5和6.0mg/L。疗效结局包括侵袭性真菌感染相关死亡率、全因死亡率、成功治疗率和预防失败率。安全性结局包括肝毒性、神经毒性和视觉障碍事件。
共纳入21项研究，涉及1158例患者。与伏立康唑谷浓度>0.5mg/L相比，<0.5mg/L的水平显著降低了治疗成功率（风险比=0.46，95%CI 0.29-0.74）。谷浓度>3.0、>4.0、>5.5和>6.0mg/L时，肝毒性发生率显著增加。谷浓度>4.0和>5.5mg/L时，神经毒性发生率显著增加。
应将伏立康唑水平0.5mg/L视为与疗效相关的下限阈值。谷浓度>3.0mg/L与肝毒性增加相关，尤其是亚洲人群，>4.0mg/L与神经毒性增加相关。
