Combined impact of hypoalbuminemia and pharmacogenomic variants on voriconazole trough concentration: data from a real-life clinical setting in the Chinese population

Abstract

Voriconazole (VRC) displays highly variable pharmacokinetics impacting treatment efficacy and safety. To provide evidence for optimizing VRC therapy regimens, the authors set out to determine the factors impacting VRC steady-state trough concentration (C_min) in patients with various albumin (Alb) level. A total of 275 blood samples of 120 patients and their clinical characteristics and genotypes of CYP2C19, CYP3A4, CYP3A5, CYP2C9, FMO3, ABCB1, POR, NR1I2 and NR1I3 were included in this study. Results of multivariate linear regression analysis demonstrated that C-reactive protein (CRP) and total bilirubin (T-Bil) were predictors of the VRC C_min adjusted for dose in patients with hypoalbuminemia (Alb < 35 g/L) (R² = 0.16, P < 0.001). Additionally, in patients with normal albumin level (Alb ≥ 35 g/L), it resulted in a significant model containing factors of the poor metabolizer (PM) CYP2C19 genotype and CRP level (R² = 0.26, P < 0.001). Therefore, CRP and T-Bil levels ought to receive greater consideration than genetic factors in patients with hypoalbuminemia.

Keywords:

• Voriconazole
• hypoalbuminemia
• CYP2C19
• gene polymorphisms
• pharmacokinetics

Authors’ contributions

Lin H. made contributions to conception and design. J.B. and J.Z. helped with the acquisition of data. Lei H., and X.H. performed the extraction of genomic DNA and genotyping. Y.L. and Ying Z. performed the statistical analysis, interpreted the data and wrote the manuscript. Yinyu Z. drew the figures and tables. B.L. and F.L. helped to revise the manuscript. Y.F. and C.Y. were involved in revising it critically for important intellectual content. All authors gave final approval of the version to be published.

Data availability statement

The datasets analysed during the current study are available from the corresponding author on reasonable request.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Beijing Municipal Natural Science Foundation [grant number 7192218].