Therapeutic drug monitoring and safety of voriconazole in elderly patients

BACKGROUND Data on therapeutic drug monitoring of voriconazole in elderly patients are limited. Impaired liver function and an inflammatory state in elderly individuals are hypothesized to impact the voriconazole serum level. METHODS A total of 166 adult patients (317 trough concentrations) who underwent voriconazole therapeutic drug monitoring were enrolled. The voriconazole trough concentration, its associated covariates, and its correlation with adverse effects in 73 elderly (≥60 years) patients (116 trough concentrations) were analyzed and compared to those in 93 adult (<60 years) patients. RESULTS The voriconazole trough concentration was 4.31 ± 3.03 μg/mL (range, 0.4-15.5 μg/mL) in the elderly patients, which was significantly higher than the 3.11 ± 2.13 μg/mL (range, 0.4-14.3 μg/mL) in the adult patients (P = 0.001). The proportion of voriconazole trough concentrations higher than 5 μg/mL was 35.3% in the elderly patients, which was also significantly higher than the 15.4% in the adult patients (P < 0.001). A stepwise multivariable linear regression model showed that procalcitonin and gamma-glutamyl transpeptidase were independently associated factors in the elderly patients (OR = 2.590, 95% confidence interval [CI] = 1.506-3.673, P = 0.001; OR = -0.016, 95% CI = -0.027 to -0.006, P = 0.005). Receiver operating characteristic (ROC) curve analysis indicated that procalcitonin concentrations of ≥1.31 ng/mL increased the incidence of a voriconazole trough concentration higher than 5 μg/mL (95% CI = 0.53-0.87 μg/mL) (P = 0.03). The incidence of decreased albumin concentrations was higher in the elderly cohort than that in the adult cohort independent of the voriconazole trough concentration (P < 0.05). CONCLUSIONS The voriconazole trough concentrations in the elderly patients were significantly higher than those in the adult patients who received voriconazole therapy and were significantly affected by severe inflammation as evaluated by the procalcitonin concentration. Frequent monitoring of the voriconazole serum concentration and procalcitonin concentration during and after severe inflammation is critical to maintain the voriconazole serum concentration within the therapeutic range.