1. ¹Pharmacy Department, Northwestern Memorial Hospital, Chicago, IL, USA
2. ²Hematopoietic Stem Cell Transplant Program, Division of Hematology/Oncology, The Feinberg School of Medicine, The Robert H Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA
3. ³Department of Pathology, Fungus Testing Laboratory, University of Texas Health Science Center, San Antonio, TX, USA
4. ⁴Division of Infectious Diseases, The Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

Correspondence: Dr J Mehta, Division of Hematology/Oncology, Northwestern University Medical School, 676 North St Clair Street, Suite 850, Chicago, IL 60611, USA. E-mail: j-mehta@northwestern.edu

Received 1 July 2004; Accepted 19 November 2004; Published online 17 January 2005.

Abstract

Voriconazole, a new antifungal agent, is increasingly being used after HSCT. The hepatic cytochrome P450 isoenzyme 2C19 plays a significant role in voriconazole metabolism. As CYP2C19 exhibits significant genetic polymorphism, some patients metabolize voriconazole poorly resulting in increased plasma drug levels. The clinical significance of this is unknown, and the utility of monitoring voriconazole levels is unclear. Steady-state trough plasma voriconazole levels were obtained in 25 allogeneic HSCT recipients using an HPLC assay. Patients had drug levels checked once (n=13), twice (n=10), or 3 times (n=2) 5–18 days (median 10) after starting voriconazole or dose modification. The 41 voriconazole levels were 0.2–6.8 g/ml (median 1.6); 6 (15%) were <0.5 (possibly below the in vitro MIC₉₀ for Aspergillus spp.). Voriconazole concentrations correlated with aspartate aminotranferase (AST) (r=0.5; P=0.0009) and alkaline phosphatase (r=0.34; P=0.03), but not with creatinine, bilirubin and alanine aminotransferase (ALT). Since liver dysfunction is common after HSCT, it was not possible to determine if elevated AST and alkaline phosphatase levels were the cause or the consequence of higher voriconazole levels. We conclude that trough voriconazole levels vary considerably between patients, and suggest monitoring levels in patients receiving voriconazole for confirmed fungal infections, and in those with elevated AST or alkaline phosphatase levels.