VALID regimen of voriconazole optimizes therapeutic target attainment and minimizes adverse events in patients with liver dysfunction.

OBJECTIVE: Liver dysfunction affects drug metabolism, including voriconazole, used for treating fungal infections. This study evaluated the effectiveness and safety of a voriconazole dosing regimen adjusted for liver dysfunction (VALID) compared with routine clinician-directed dosing. METHODS: This observational, non-interventional study included hospitalized patients with clinically diagnosed liver dysfunction, mainly including liver cirrhosis and acute-on-chronic liver failure, who received voriconazole for the prevention or treatment of invasive fungal infection between January 2020 and December 2023. Patients were assigned to the VALID or control group according to their actual initial dosing regimen. Propensity score matching was performed using 1:1 nearest-neighbor matching without replacement and a caliper value of 0.05. Voriconazole trough concentrations were measured using liquid chromatography. CYP2C19 phenotype, when available, and liver function-related indicators were assessed as covariates influencing voriconazole exposure. RESULTS: A total of 182 patients with liver dysfunction and 375 voriconazole trough concentration measurements were initially included, including 39 patients in the VALID group and 143 patients in the control group. After propensity score matching, 39 patients from each group were included for between-group comparisons. The VALID group had a significantly higher initial target trough concentration attainment rate than the control group (89.7% vs. 48.7%, P < 0.001) and a lower initial trough concentration [2.46 (1.85-3.04) mg/L vs. 4.13 (2.78-6.48) mg/L, P = 0.0003]. The VALID group also had a lower incidence of voriconazole-related adverse events (15.4% vs. 38.5%, P = 0.022), while clinical efficacy and dose adjustment did not differ significantly between the two groups. CYP2C19 phenotype, liver function-related indicators, coagulation-related indicators, and daily dose were associated with voriconazole trough concentrations. CONCLUSION: The TBIL-based VALID regimen showed potential to improve target trough concentration attainment and reduce voriconazole-related adverse events in patients with liver dysfunction while maintaining comparable efficacy. However, this regimen should be interpreted as a preliminary initial dosing strategy and still requires validation in larger multicenter prospective studies. TDM and individualized dose adjustment remain necessary during treatment.