# Personalizing voriconazole dosing in Chinese hematological patients: CYP2C19 phenotype and albumin-bilirubin grade as key predictors of trough concentrations

## TL;DR

The study finds that genetic factors like CYP2C19 and liver function (ALBI grade) strongly influence voriconazole levels in Chinese blood disease patients, helping personalize dosing.

## Contribution

Identifies CYP2C19 phenotype and ALBI grade as key predictors for voriconazole trough concentrations in Chinese hematological patients.

## Key findings

- Poor metabolizers of CYP2C19 had significantly higher dose-normalized voriconazole trough concentrations.
- ALBI grade 3 patients showed significantly higher voriconazole trough concentrations compared to lower grades.
- Sex, glucocorticoid use, creatinine clearance, and CYP2C19 genotype were significant predictors of voriconazole trough levels.

## Abstract

This retrospective, single-center study aimed to evaluate the genetic and non-genetic factors influencing voriconazole (VRC) trough concentration (C
trough), efficacy and safety in hematological patients.

Medical records of inpatients were reviewed retrospectively. Univariate and multivariate analyses were performed to identify factors contributing to the variability of VRC C
trough.

A total of 375 VRC C
trough measurements from 89 patients were analyzed. At the time of the initial C
trough assessment, 74 patients (83.1%) received oral VRC, while 15 patients (16.9%) received intravenous VRC. Among these first C
trough measurements, 68.5% of patients achieved the target therapeutic range (1.0–5.5 mg/L), whereas 28.1% had subtherapeutic concentrations and 3.4% had supratherapeutic concentrations. The dose-normalized VRC C
trough (C
trough/D) were significantly higher in poor metabolizers (PMs) compared to normal metabolizers (NMs) (P = 0.001) and intermediate metabolizers (IMs) (P = 0.021). The albumin-bilirubin (ALBI) grade, a novel liver function assessment tool, was significantly associated with VRC C
trough/D. Patients with ALBI grade 3 had significantly higher C
trough/D values compared to those with grade 2 (P = 0.001) and grade 1 (P < 0.001). The linear mixed model revealed that sex, concomitant glucocorticoid use, creatinine clearance rate (Ccr), CYP2C19 genotype, and ALBI grade were statistically significant predictors of VRC C
trough/D. A total of 10 patients (11.2%) had their VRC dosage adjusted based on therapeutic drug monitoring (TDM). The overall treatment success rate was 75.3% (67/89). Adverse drug reactions (ADRs) were observed in 12 patients (13.5%) during VRC therapy.

CYP2C19 phenotype, ALBI grade, sex, Ccr and concomitant use of glucocorticoids contribute to the variability of VRC C
trough and should be comprehensively considered when determining VRC dosage in Chinese hematological patients.