Infection and Drug Resistance (Aug 2018)
Trough concentration of itraconazole and its relationship with efficacy and safety: a systematic review and meta-analysis
Abstract
Jingru Zhang,1,2 Yiwei Liu,1 Xiaolu Nie,1 Yuncui Yu,1 Jian Gu,3 Libo Zhao1 1Clinical Research Center, Beijing Children’s Hospital, Capital Medical University, Beijing, China; 2Department of Pharmacy Administration and Clinical Pharmacy, Peking University School of Pharmaceutical Sciences, Beijing, China; 3Department of Pharmacy, Peking University People’s Hospital, Beijing, China Objectives: 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.Methods: We searched PubMed, EMBASE, Web of Science, the Cochrane Library, ClinicalTrials.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.Results: The study included a total of 29 studies involving 2,346 patients. Our meta-analysis showed that compared with itraconazole trough concentrations (Ctrough) 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.Conclusion: 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]). Keywords: itraconazole, trough concentration, efficacy, safety, meta-analysis
