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Voriconazole plasma monitoring
  1. A C Pasqualotto1,2,
  2. M Shah3,
  3. R Wynn4,
  4. D W Denning1,2,5
  1. 1
    School of Medicine, University of Manchester, UK
  2. 2
    Wythenshawe Hospital, Manchester, UK
  3. 3
    Burn Unit, Booth Hall Children’s Hospital, Manchester, UK
  4. 4
    Department of Haematology, Royal Manchester Children’s Hospital, Manchester, UK
  5. 5
    Regional Mycology Laboratory, Manchester, UK
  1. Alessandro Pasqualotto, Education and Research Centre, Wythenshawe Hospital, Southmoor Road, Manchester, M23 9LT, UK; acpasqualotto{at}hotmail.com

Abstract

Aims: Very little information is available regarding the use of voriconazole drug monitoring in children with invasive fungal infections. The purpose of this study was to report the cases of five paediatric patients treated with voriconazole, in which plasma levels were used to monitor therapy.

Methods: Five children treated with voriconazole were included in this case series. Voriconazole plasma levels were determined using either a bioassay or liquid chromatography–tandem mass spectrometry.

Results: The patients’ ages ranged from 2 to 10 years old (mean 6.2 years). Three patients had acute leukaemia and two had suffered severe burn injuries. Doses administered varied from 3.4 mg/kg every 12 h to 8.1 mg/kg every 8 h. Plasma voriconazole concentrations were unpredictable for these paediatric patients. Subtherapeutic levels were frequently observed, despite progressive increments in dosage. For others, voriconazole levels markedly increased after a small increment in dosage. Phenobarbitone caused important drug interactions with voriconazole for two of the patients.

Conclusions: The dose administered did not correlate with exposure as measured by plasma levels of voriconazole. While the optimal dosage for voriconazole in children is still unknown, drug monitoring seems warranted to ensure adequate exposure, and after dose increments to prevent excessive exposure. Drug interactions significantly altered exposure.

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Footnotes

  • Funding: ACP receives a grant from CAPES (Brazilian government).

  • Competing interests: In the past 5 years, DWD has received grant support from Astellas, Merck, Pfizer, F2G, OrthoBiotech, Indevus, Basilea, the Fungal Research Trust, the Wellcome Trust, the Moulton Trust, The Medical Research Council, the National Institute of Allergy and Infectious Diseases and the European Union. He has been an advisor/consultant to Basilea, Vicuron (now Pfizer), Schering Plough, Indevus, F2G, Nektar, Daiichi, Sigma Tau, Astellas, Gilead and York Pharma. He has been paid for talks on behalf of Astellas, Merck, GSK, Chiron, AstraZenca and Pfizer. He holds founder shares in F2G Ltd and Myconostica Ltd, both university spin-out companies. Myconostica is engaged in commercialising molecular diagnostics for infectious diseases, including invasive fungal infections.

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