Association of Voriconazole Trough Plasma Concentration with Efficacy and Incidence of Hepatotoxicity in Iranian Patients with Hematological Malignancies

Document Type : Research article


1 Department of Clinical Pharmacy, Faculty of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran.

2 Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

3 Research Center for Rational Use of Drugs, Tehran University of Medical Sciences, Tehran, Iran.

4 Hematology-Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.


There are conflicting data regarding the association between plasma concentration of voriconazole (VCZ) and both efficacy and safety. This study investigates the association of VCZ trough plasma level with clinical efficacy and hepatotoxicity in the Iranian population suffering hematological malignancies. This cross-sectional study was performed on adult Iranian patients (age ≥ 18 years) with hematological malignancies undergoing treatment with oral or intravenous VCZ for proven or probable invasive aspergillosis. Plasma concentrations of VCZ were measured at two time points on day 4 and 14 during the study period. A total of 60 VCZ trough concentrations of 30 patients were drawn on days 4 and 14 after the initiation of treatment. There was no definite correlation between the mean plasma concentration of VCZ and VCZ dosage (p = 0.134, r = 0.280). In multivariable model, only plasma concentration of VCZ on day 14 was associated with the incidence of hepatotoxicity (p = 0.013; OR = 1.42, 95% CI = 1.07-3.24). Plasma trough concentration neither on day 4 nor on day 14 was related to the treatment response. No significant association was observed between the mean plasma concentration of VCZ and 3-month patients’ survival (p = 0.696). To conclude, VCZ trough concentration may not be a predictor of treatment response or 3-month patients’ survival. However, the wide inter- and intra-patient variability of VCZ plasma concentration coupled with the observed association between VCZ trough level and the incidence of hepatotoxicity would pose the question regarding the potential benefit of VCZ concentration monitoring.

Graphical Abstract

Association of Voriconazole Trough Plasma Concentration with Efficacy and Incidence of Hepatotoxicity in Iranian Patients with Hematological Malignancies


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