Autoinduction of voriconazole metabolism in a child with invasive pulmonary aspergillosis. Pharmacotherapy 2015 Apr;35(4):e20-6
Date
04/18/2015Pubmed ID
25884532DOI
10.1002/phar.1566Scopus ID
2-s2.0-84927757197 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
Inter- and intra-patient variability in voriconazole pharmacokinetics has been described in children as the result of age-specific differences in hepatic metabolism, saturable nonlinear pharmacokinetics, CYP450 2C19 polymorphisms, decreased bioavailability compared with adults, and drug-drug interactions. We introduce dose-dependent autoinduction of metabolism as another cause for altered voriconazole pharmacokinetics in children and summarize previously published literature on this phenomenon. A 10-year-old girl with severe aplastic anemia developed invasive pulmonary aspergillosis after high-dose cyclophosphamide therapy and required high doses of voriconazole for longer than 2 months. She initially achieved a therapeutic trough of 1.4 μg/ml on voriconazole 11 mg/kg/dose orally every 12 hours but required dose escalations to 9.3 mg/kg/dose orally every 8 hours to maintain a trough above 1 μg/ml. Because there were no changes in concomitant medications, route of administration, adherence, or oral intake, we conclude that the only plausible explanation for the precipitous drop in voriconazole troughs was autoinduction of metabolism, a phenomenon previously reported in adults receiving higher than usual doses or prolonged courses (longer than 2 months). These data highlight the need for continued therapeutic drug monitoring of voriconazole after initial therapeutic troughs are achieved because autoinduction of metabolism can lead to significant declines in subsequent voriconazole troughs, potentially leading to treatment failure.
Author List
Hsu AJ, Dabb A, Arav-Boger RAuthor
Ravit Boger MD Chief, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Anemia, AplasticAntifungal Agents
Antineoplastic Agents, Alkylating
Child
Cyclophosphamide
Female
Humans
Immunocompromised Host
Invasive Pulmonary Aspergillosis
Voriconazole
