Trough concentration of itraconazole and its relationship with efficacy and safety: a systematic review and meta-analysis

Abstract

Trough concentration of itraconazole and its relationship with efficacy and safety: a systematic review and meta-analysis 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 (