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

Yichang Zhao1,2, Jingjing Hou1,2, Yiwen Xiao1,2

  • 1The Second Xiangya Hospital, Central South University, Changsha 410011, China.

Antibiotics (Basel, Switzerland)
|September 28, 2021
PubMed

Insights

Voriconazole trough concentrations in Child-Pugh class C patients varied significantly, with dose adjustments and CYP2C19 genotyping impacting levels. Therapeutic drug monitoring is crucial for safe voriconazole administration in these patients.

Area of Science:

  • Pharmacology
  • Hepatology
  • Clinical Pharmacy

Background:

  • Voriconazole is a critical antifungal agent, but its use in patients with severe liver disease (Child-Pugh class C) lacks clear dosing guidelines.
  • Understanding voriconazole pharmacokinetics in Child-Pugh class C patients is essential for optimizing treatment and minimizing toxicity.
  • Variability in voriconazole trough concentrations can lead to subtherapeutic levels or supratherapeutic accumulation, impacting efficacy and safety.

Purpose of the Study:

  • To describe voriconazole administration and trough concentrations in Child-Pugh class C patients.
  • To investigate the variability and influencing factors of voriconazole trough concentrations in this specific population.
  • To assess the utility of CYP2C19 genotyping for personalized voriconazole dosing.

Main Methods:

  • Prospective observational study analyzing 144 voriconazole trough concentrations from 43 Child-Pugh class C patients.
  • Bivariate correlation and stepwise multiple linear regression analyses were performed to identify factors affecting concentration.
  • Key factors analyzed included sex, CYP2C19 genotyping, daily dose, prothrombin time activity, international normalized ratio, platelet count, and MELD score.

Main Results:

  • The majority of patients (62.8%) required dose adjustments.
  • Repeatedly measured trough concentrations were generally higher than initial and final measurements, suggesting potential accumulation.
  • Significant factors influencing voriconazole concentration included sex, CYP2C19 genotype, daily dose, PT activity, INR, platelets, and MELD score. The developed regression model explained 34.8% of the concentration variability.

Conclusions:

  • Voriconazole administration in Child-Pugh class C patients requires careful clinical management due to a lack of specific label recommendations.
  • Therapeutic drug monitoring is vital for adjusting voriconazole regimens in this population.
  • CYP2C19 genotyping shows promise for guiding precision medicine approaches in Child-Pugh class C cirrhosis patients.

Keywords:
CYP2C19Child–Pugh C cirrhosisadministrationtrough concentrationsvoriconazole

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