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Monitoring plasma voriconazole levels may be necessary to avoid subtherapeutic levels in hematopoietic stem cell transplant recipients
Author(s) -
Trifilio Steve,
Pennick Gennethel,
Pi Judy,
Zook Jennifer,
Golf Mary,
Kaniecki Kimberley,
Singhal Seema,
Williams Stephanie,
Winter Jane,
Tallman Martin,
Gordon Leo,
Frankfurt Olga,
Evens Andrew,
Mehta Jayesh
Publication year - 2007
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.22568
Subject(s) - voriconazole , medicine , hematopoietic stem cell transplantation , gastroenterology , therapeutic drug monitoring , trough level , trough concentration , transplantation , pharmacokinetics , tacrolimus , antifungal , dermatology
BACKGROUND. Low voriconazole levels have been associated with a higher failure rate in patients with confirmed fungal infections. METHODS. Steady‐state plasma trough voriconazole levels were measured after at least 5 days of therapy in 87 patients with hematologic malignancies on 201 separate occasions (1–5 levels per patient; median, 2). Most patients (90%) had undergone allogeneic hematopoietic stem cell transplantation. The daily voriconazole dose, administered in 2 divided doses, was 200 mg (n = 4), 400 mg (n = 151), 500 mg (n = 20), 600 mg (n = 18), and 800 mg (n = 8); corresponding to 2.0–16.3 (median, 5.4) mg/kg. Plasma voriconazole levels were 0–12.5 μg/mL (median, 1.2). Voriconazole was undetectable (<0.2 μg/mL) in 15%. RESULTS. The correlation between dose and levels was weak ( r = 0.14; P = .045). The median absolute daily drug dose (400 mg) was identical in groups of patients with levels of 0, 0.2 to 0.5, >0.5 to 2.0, >2.0 to 5.0, and >5.0. Whereas the daily drug dose in mg/kg was significantly higher when the levels were >5.0 μg/mL, there was no consistent relation between dose and level below that threshold. In adult patients getting standard doses of voriconazole orally, the drug levels are highly variable. Based on limited available data, between a quarter and two‐thirds of these levels could potentially be associated with a lower likelihood of response or a higher likelihood of failure. CONCLUSIONS. Future voriconazole studies should incorporate prospective therapeutic drug monitoring and consideration should be given to checking levels in patients receiving the drug for confirmed, life‐threatening fungal infections. Cancer 2007. © 2007 American Cancer Society.