Working Paper Article Version 1 This version is not peer-reviewed

Predictors of Voriconazole trough Concentrations in Patients with Child-Pugh Class C Cirrhosis: A Prospective Study

Version 1 : Received: 11 August 2021 / Approved: 12 August 2021 / Online: 12 August 2021 (15:33:44 CEST)

A peer-reviewed article of this Preprint also exists.

Zhao, Y.; Hou, J.; Xiao, Y.; Wang, F.; Zhang, B.; Zhang, M.; Jiang, Y.; Li, J.; Gong, G.; Xiang, D.; Yan, M. Predictors of Voriconazole Trough Concentrations in Patients with Child–Pugh Class C Cirrhosis: A Prospective Study. Antibiotics 2021, 10, 1130. Zhao, Y.; Hou, J.; Xiao, Y.; Wang, F.; Zhang, B.; Zhang, M.; Jiang, Y.; Li, J.; Gong, G.; Xiang, D.; Yan, M. Predictors of Voriconazole Trough Concentrations in Patients with Child–Pugh Class C Cirrhosis: A Prospective Study. Antibiotics 2021, 10, 1130.

Journal reference: Antibiotics 2021, 10, 1130
DOI: 10.3390/antibiotics10091130

Abstract

This prospective observational study aimed to describe voriconazole administrations and trough concentrations in patients with Child-pugh class C clinically, and to investigate the variability of trough concentration. A total of 144 voriconazole trough concentrations from 43 Child-pugh class C patients were analyzed. The majority of patients (62.8%) received adjustments. The repeated measured trough concentration was higher than the first and final ones generally (median, 4.33 vs. 2.99, 3.90 mg/L). Eight patients with ideal initial concentration later got supratherapeutic with no adjusted daily dose, implying accumulation. There was a significant difference in concentrations among the six groups by daily dose (P=0.006). The bivariate correlation analysis showed that sex, CYP2C19 genotyping, daily dose, prothrombin time activity, international normalized ratio, platelet, and Model for end-stage liver disease score were significant factors for concentration. Subsequently, the first four factors mentioned above entered into a stepwise multiple linear regression model (variance inflation factor < 5), implying that CYP2C19 testing makes sense for precision medicine of Child-pugh class C cirrhosis patients. The equation fits well and explains the 34.8% variety of concentrations (R^2 = 0.348). In conclusion, it needs more cautious administration clinically due to no recommendation for Child-pugh class C patients in the medication label. The adjustment of the administration regimen should be mainly based on the results of repeated therapeutic drug monitoring.

Keywords

Child-pugh C cirrhosis; voriconazole; trough concentrations; administration; CYP2C19

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