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Therapeutic drug monitoring of voriconazole and CYP2C19 phenotype for dose optimization in paediatric patients

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Abstract

Purpose

The objective of this study was to evaluate factors influencing voriconazole (VRC) plasma trough concentrations and provide research data for optimizing VRC dosing in Chinese paediatric patients.

Methods

Medical records of inpatients were reviewed retrospectively. Multivariate linear regression analysis was used to identify the factors contributing to the variability of VRC plasma trough concentrations.

Results

A total of 250 VRC plasma trough concentrations from 131 paediatric patients were included in the analysis. The median VRC plasma trough concentration was 1.28 mg·L−1 (range, 0.02 to 9.69 mg·L−1). The target range was achieved in 51.6% of patients, while subtherapeutic and supratherapeutic concentrations were obtained in 40.4% and 8.0% of paediatric patients, respectively. The most commonly identified cytochrome P450 2C19 (CYP2C19) phenotype was intermediate metabolizers (IMs) (48.9%), followed by normal metabolizers (NMs) (40.5%) and poor metabolizers (PMs) (10.7%), but no ultrarapid metabolizers (UMs) were observed in our study. VRC plasma trough concentrations adjusted for dose (Cmin/D) were significantly lower in both NMs and IMs compared to PMs (PN-P < 0.001 and PI-P = 0.010, respectively). The dosage of VRC required to achieve the therapeutic range was related to age, with children aged < 6 years needing a significantly higher oral dose of VRC. The oral and intravenous maintenance doses needed to reach the therapeutic range were significantly lower than the recommended maintenance dose (P < 0.001, P < 0.001). Factors such as CYP2C19 polymorphisms, the combination of omeprazole, levels of albumin and alanine aminotransferase, were found to affect VRC exposure and explained some of the variability.

Conclusions

The VRC plasma trough concentration is significantly influenced by the CYP2C19 phenotype. The recommended maintenance dose for pediatric patients may not be appropriate for Chinese patients. To increase the probability of achieving the therapeutic range for VRC plasma trough concentration, the administration of VRC should consider the age of paediatric patients and the presence of CYP2C19 polymorphisms.

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Acknowledgements

We appreciate the professional comments from the reviewers, which greatly improved our manuscript.

Author information

Authors and Affiliations

  1. Department of Pharmacy, the First Hospital of Changsha, Changsha, Hunan, China

    Lin Hu & Shiqiong Huang

  2. Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Qi Huang

  3. Clinical Trial Institution Office, Liuzhou Hospital of Guangzhou Women and Children’s Medical Center, Liuzhou, Guangxi, China

    Zeying Feng

  4. Center of Clinical Pharmacology, the Third Xiangya Hospital, Central South University, Changsha, Hunan, China

    Zeying Feng

Authors
  1. Lin Hu
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Contributions

Lin Hu wrote the main manuscript text and Shiqiong Huang collected the data. Qi Huang provided laboratory data and Zeying Feng revised the manuscript. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Lin Hu or Zeying Feng.

Ethics declarations

Ethics approval

This study strictly followed the Helsinki Declaration, and the protocol was approved by the Institutional Review Board of Xiangya Hospital (approval number 2018091069).

Consent to participate

Written informed consent was obtained from all participants for the TDM of VRC, the measurement of CYP2C19 phenotype, and the use of their data.

Consent for publication

The identity information of all patients was coded to ensure privacy was not compromised.

Competing interest

The authors have declared that no competing interests exist.

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Hu, L., Huang, Q., Huang, S. et al. Therapeutic drug monitoring of voriconazole and CYP2C19 phenotype for dose optimization in paediatric patients. Eur J Clin Pharmacol 79, 1271–1278 (2023). https://doi.org/10.1007/s00228-023-03538-9

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  • DOI: https://doi.org/10.1007/s00228-023-03538-9

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