A C Pasqualotto1, M Shah, R Wynn, D W Denning. 1. Alessandro Pasqualotto, Education and Research Centre, Wythenshawe Hospital, Southmoor Road, Manchester, M23 9LT, UK. acpasqualotto@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 one [corrected] 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.
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 one [corrected] 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.
Authors: Kevin Watt; Paolo Manzoni; Michael Cohen-Wolkowiez; Stefano Rizzollo; Elena Boano; Evelyne Jacqz-Aigrain; Daniel K Benjamin Journal: Curr Drug Metab Date: 2013-02 Impact factor: 3.731
Authors: Chris Stockmann; Jonathan E Constance; Jessica K Roberts; Jared Olson; Elizabeth H Doby; Krow Ampofo; Justin Stiers; Michael G Spigarelli; Catherine M T Sherwin Journal: Clin Pharmacokinet Date: 2014-05 Impact factor: 6.447