| Title | Trough concentration of itraconazole and its relationship with efficacy and safety: a systematic review and meta-analysis |
| Authors | Zhang, Jingru Liu, Yiwei Nie, Xiaolu Yu, Yuncui Gu, Jian Zhao, Libo |
| Affiliation | Capital Med Univ, Beijing Childrens Hosp, Clin Res Ctr, 56 Nanlishi Rd, Beijing 100045, Peoples R China. Peking Univ, Sch Pharmaceut Sci, Dept Pharm Adm & Clin Pharm, Beijing, Peoples R China. Peking Univ, Peoples Hosp, Dept Pharm, Beijing, Peoples R China. |
| Keywords | itraconazole trough concentration efficacy safety meta-analysis INFECTIOUS-DISEASES-SOCIETY HEMATOPOIETIC STEM-CELL ACQUIRED-IMMUNODEFICIENCY-SYNDROME INVASIVE FUNGAL-INFECTIONS ESCMID-ASTERISK GUIDELINE CLINICAL-PRACTICE GUIDELINES RANDOMIZED CONTROLLED-TRIAL IN-VITRO ACTIVITIES ANTIFUNGAL PROPHYLAXIS NEUTROPENIC PATIENTS |
| Issue Date | 2018 |
| Publisher | INFECTION AND DRUG RESISTANCE |
| Citation | INFECTION AND DRUG RESISTANCE. 2018, 11, 1283-1297. |
| Abstract | 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, 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. Results: The study included a total of 29 studies involving 2,346 patients. Our meta-analysis showed that compared with itraconazole trough concentrations (C-trough) 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]). |
| URI | http://hdl.handle.net/20.500.11897/524851 |
| ISSN | 1178-6973 |
| DOI | 10.2147/IDR.S170706 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 药学院 人民医院 |
