Therapeutic drug monitoring and safety evaluation of Voriconazole in the
treatment of pulmonary fungal diseases
Abstract
Aims: To investigate the relationship between steady-state voriconazole
trough concentration (Ctrough) and adverse effects (AEs). Methods: We
conducted a retrospective study in the Jinling Hospital from January
2015 to June 2020. A total of 140 patients receiving voriconazole were
enrolled in this study. The determination and scoring of
voriconazole-associated hepatotoxicity were performed according to the
Roussel Uclaf Causality Assessment Method scoring scale and the severity
of hepatotoxicity was graded according to CTCAE. Results: Compared to
the group without any AEs, voriconazole Ctrough was significantly higher
in the hepatotoxicity and neurotoxicity groups; however, no differences
were observed in other AEs. Receiver operating characteristic (ROC)
curves showed that steady-state voriconazole Ctrough >3.61
mg/L was associated with an increased incidence of hepatotoxicity
(AUC=0.645, P=0.047). Logistic regression analysis showed that timely
voriconazole dose adjustment was a predictor of attenuated
hepatotoxicity after adjustment for confounders, but hepatotoxicity was
not associated with voriconazole Ctrough measured at a single time
point. When gamma-glutamyl transpeptidase (GGT) was included in the
assessment of hepatotoxicity severity, its AE was overestimated.
Steady-state voriconazole Ctrough and length of treatment were
associated with GGT elevation. Conclusions: Despite an increasing trend
of hepatotoxicity and neurotoxicity with increasing steady-state
voriconazole Ctrough, it may not be sufficient for predicting the
probability of hepatotoxicity. Concomitant co-monitoring of liver
function parameters for 2 weeks after dosing may provide greater
prevention of hepatotoxic events. In patients with long-term
voriconazole usage, GGT is not a reliable indicator of hepatotoxicity,
but it can be used to assess oxidative stress levels.