Individualized medication monitoring of voriconazole in adults

Abstract:

Objective According to the trough concentration，anti-infective efficacy，and hepatotoxicity of voriconazole in Individualized Medication of Voriconazole：A Practice Guideline of the Division of Therapeutic Drug Monitoring， the judgment based on medium-quality evidence cannot meet clinical needs. This article will perform dynamic monitoring of the trough concentration of voriconazole in adult inpatients to investigate the association of trough concentration with therapeutic efficacy and adverse reactions.Methods A total of 107 blood samples were collected from 63 adult patients who were treated with voriconazole， and enzyme immunoassay was used for dynamic monitoring of the trough concentration of voriconazole. The patients were observed in terms of treatment outcome and adverse reactions，and the correlation of the trough concentration of voriconazole with clinical indices was analyzed.Results After treatment with voriconazole at the conventional dose，the trough concentration of voriconazole was 0.5-5.0 μg/mL in 57.9%（62/107） of the samples，with a averge concentration of 2.7 μg/mL；the trough concentration of voriconazole was <0.5 μg/mL in 3.7%（4/107） of the samples，with a averge concentration of 0.3 μg/mL；the trough concentration of voriconazole was >5.0 μg/mL in 38.4% （41/107） of the samples，with a median concentration of 8.7 μg/mL. The patients with a trough concentration of <0.5 μg/mL had a response rate of 50.0%，while those with a trough concentration of ≥0.5 μg/mL had a response rate of 74.5%，and there was no significant difference between the two groups（P=0.624）. The dose was increased for one patient who had a trough concentration of <0.5 μg/mL and had no response to treatment，and the symptoms of infection were improved after effective trough concentration was reached. Adverse reactions were observed in 10 patients（15.8%）， and the incidence rate of adverse reactions was 18.2% in patients with a trough concentration of >5.0 μg/mL and 14.6% in those with a trough concentration of ≤5.0 μg/mL， with the main adverse reaction of abnormal liver function. There were significant differences in alkaline phosphatase and gamma-glutamyl transpeptidase between the patients with a trough concentration of >5.0 μg/mL and those with a trough concentration of ≤5.0 μg/mL（P<0.05），and when the trough concentration of voriconazole was >5.0 μg/mL，there was a significant reduction in procalcitonin after anti-infective therapy（P<0.05）.Conclusion There is a large difference in the plasma concentration of voriconazole between individuals， and its trough concentration must be monitored regularly. The trough concentration of voriconazole is associated with liver function parameters and infection indicators， and it may be necessary to increase sample size or perform CYP2C19 genetic testing to observe the association of trough concentration with therapeutic efficacy and adverse reactions.