Monitor the voriconazole trough concentration of patients with pulmonary fungal infection in clinical application

Abstract

Objective Through the voriconazole trough concentrations monitoring in patients with pulmonary fungal infection, to explore the correlation between voriconazole trough concentrations and clinical efficacy and adverse reaction and characteristics in different wards. Methods Using high performance liquid chromatography-fluorescence method for the determination of voriconazole blood drug concentration, observe clinical efficacy and adverse reactions in different ward during the period of the treatment. Results 133 voriconazole trough concentrations were obtained from 87 patients, voriconazole trough concentration of first detection was (3.37±2.6) mg/L, the mean of 133 voriconazole trough concentration was (2.98±2.28) mg/L.Serum concentration of intravenous administration was higher than that of oral administration (3.30±2.61) vs (2.31±2.02) mg/L(P=0.018). There was no significant difference between the three groups in different wards: outpatients (3.06±2.2) mg/L, common ward (2.6±2.5) mg/L, ICU (3.1±2.5) mg/L, but for the same patients, outpatient′s drug concentrations fluctuatesmallerly, ICU patient′s blood drug concentrations fluctuate greatly.68 of 87 patients (78%) were treated successfully.There was no statistical significance of the voriconazole trough concentrations between successful treatment group and the failure.The number of samples with voriconazole concentrations below 1 mg/L was higher in patients who exhibited therapeutic failures (36.8% vs 14.7%, P=0.048). Hypokalemia occurred in 28 of 87 paients(32%), hepatic lesion (14%), AKI (3.4%), rash (3.4%), visual disorder (2%). Visual disorder and hepatic lesion were significantly associated with high blood drug concentration (P<0.05). Conclusions Voriconazole trough concentrations fluctuate range, voriconazole trough concentration of first detection was (3.37±2.6) mg/L (0~11.3) mg/L.There was no significant correlation between serum concentration and clinical efficacy, and we found that lack of response was more frequent in patients with levels lower than 1 mg/L.Visual disorder and hepatic lesion were associated with higher voriconazole trough concentrations.We suggest that the therapeutic range for voriconazole should be (1~5) mg/L.Voriconazole trough concentrations should be monitoring in different wards, especially in ICU, adjust timely to reduce adverse drug incidences. Key words: Voriconazole; Therapeutic drug monitoring; Adverse drug reactions; Pulmonary fungal infection