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Therapeutic Drug Monitoring of Voriconazole in Critically Ill Pediatric Patients: A Single-Center Retrospective Study

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Abstract

Background and Objective

Voriconazole pharmacokinetics are highly variable in pediatric patients, and the optimal dosage has yet to be determined. The purpose of this study was to describe voriconazole pharmacokinetic and pharmacodynamic targets achieved and evaluate the efficacy and safety of voriconazole for critically ill pediatrics.

Methods

This is a single-center retrospective study conducted at a pediatric intensive care unit at a tertiary/quaternary hospital. Pediatrics admitted to the pediatric intensive care unit and who received voriconazole for a proven or suspected fungal infection with at least one measured trough concentration were included. The primary outcomes included the percentage of pediatric patients who achieved the pharmacokinetic and pharmacodynamic targets. Secondary outcomes included assessing the correlation between voriconazole trough concentrations and clinical/microbiological outcomes. All statistical analyses were performed using the R statistical software and Microsoft Excel. Multiple logistic regression was used to assess the predictors of both clinical and microbiologic cures. Multiple linear regression was used to determine significant factors associated with trough concentrations.

Results

A total of 129 voriconazole trough concentrations were measured from 71 participants at steady state after at least three doses of voriconazole. The mean (± standard deviation) of the first and second trough concentrations were 2.9 (4.2) and 2.3 (3.3) mg/L, respectively. Among the first trough concentrations, only 33.8% were within the therapeutic range (1–5 mg/L), 46.5% were below the therapeutic range, and 19.7% were above the therapeutic range. A clinical cure occurred in 78% of patients, while a microbiologic cure occurred in 80% of patients.

Conclusions

Voriconazole trough concentrations vary widely in critically ill pediatric patients and only a third of the patients achieved therapeutic concentrations with initial doses.

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Acknowledgements

We thank Ms. Rania Aljaber, a senior pharmacy specialist from the pharmacy automation team at the King Faisal Specialist Hospital and Research Center, for her assistance in retrieving the patients’ data.

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Authors and Affiliations

  1. Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, MBC 11, P.O. Box 3354, 11211, Riyadh, Saudi Arabia

    Khalid W. Taher & Razan Almofada

  2. Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

    Sufyan Alomair

  3. Department of Pharmacy Practice, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia

    Sufyan Alomair

  4. Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia

    Ahmed A. Albassam

  5. Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia

    Abdullah Alsultan

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  1. Khalid W. Taher
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Corresponding author

Correspondence to Khalid W. Taher.

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Funding

No funding was received for the conduct of this study.

Conflicts of interest/competing interests

Khalid W. Taher, Razan Almofada, Sufyan Alomair, Ahmed A. Albassam, and Abdullah Alsultan have no conflicts of interest that are directly relevant to the content of this article.

Ethics approval

The study was approved by the King Faisal Specialist Hospital & Research Centre Institutional Review Board (No. 2221242).

Consent to participate

Not applicable.

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Not applicable.

Availability of data and material

The King Faisal Specialist Hospital & Research Centre provided the study data; however, there are restrictions on its availability. These data were used under license for the current study and are not available publicly. However, upon reasonable request and with permission from the King Faisal Specialist Hospital & Research Centre, the authors could provide data.

Code availability

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Authors’ contributions

RA and SA worked on the data collection. AAA and AA worked on the data analysis. All authors worked on designing the study, writing the manuscript, and reviewing the final version of the manuscript.

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Taher, K.W., Almofada, R., Alomair, S. et al. Therapeutic Drug Monitoring of Voriconazole in Critically Ill Pediatric Patients: A Single-Center Retrospective Study. Pediatr Drugs 26, 197–203 (2024). https://doi.org/10.1007/s40272-023-00616-4

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  • DOI: https://doi.org/10.1007/s40272-023-00616-4

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