Enhancing voriconazole therapy in liver dysfunction: exploring administration schemes and predictive factors for trough concentration and efficacy

Abstract

Introduction: The application of voriconazole in patients with liver dysfunction lacks pharmacokinetic data. In previous study, we proposed to develop voriconazole dosing regimens for these patients according to their total bilirubin, but the regimens are based on Monte Carlo simulation and has not been further verified in clinical practice. Besides, there are few reported factors that significantly affect the efficacy of voriconazole.Methods: We collected the information of patients with liver dysfunction hospitalized in our hospital from January 2018 to May 2022 retrospectively, including their baseline information and laboratory data. We mainly evaluated the efficacy of voriconazole and the target attainment of voriconazole trough concentration.Results: A total of 157 patients with liver dysfunction were included, from whom 145 initial and 139 final voriconazole trough concentrations were measured. 60.5% (95/157) of patients experienced the adjustment of dose or frequency. The initial voriconazole trough concentrations were significantly higher than the final (mean, 4.47 versus 3.90 μg/mL, p = 0.0297). Furthermore, daily dose, direct bilirubin, lymphocyte counts and percentage, platelet, blood urea nitrogen and creatinine seven covariates were identified as the factors significantly affect the voriconazole trough concentration. Binary logistic regression analysis revealed that the lymphocyte percentage significantly affected the efficacy of voriconazole (OR 1.138, 95% CI 1.016–1.273), which was further validated by the receiver operating characteristic curve.Conclusion: The significant variation in voriconazole trough concentrations observed in patients with liver dysfunction necessitates caution when prescribing this drug. Clinicians should consider the identified factors, particularly lymphocyte percentage, when dosing voriconazole in this population.

Renal Replacement Therapy as a New Indicator of Voriconazole Clearance in a Population Pharmacokinetic Analysis of Critically Ill Patients

“…However, a previous study [ 12 ] reported higher voriconazole plasma concentrations in patients with moderate renal impairment (CL CR 40–55 mL/min) than in those with normal renal function (CL CR ≥ 60 mL/min) following the administration of 320 mg and 240 mg doses. Similar findings have been reported using multiple linear regression analyses [ 30 , 31 , 44 , 45 ]. In a prospective PK study involving 105 kidney transplant recipients (342 concentrations), the reported voriconazole CL was 2.88 L/h, and the authors speculated that the low CL might be attributed to the unrecovered kidney function [ 29 ].…”