Voriconazole therapeutic drug monitoring in allogeneic hematopoietic stem cell transplant recipients

S. Trifilio, R. Ortiz, G. Pennick, Amit K. Verma, J. Pi, V. Stosor, T. Zembower, J. Mehta

Research output: Contribution to journalArticle

157 Citations (Scopus)

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 μg/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.

Original languageEnglish (US)
Pages (from-to)509-513
Number of pages5
JournalBone Marrow Transplantation
Volume35
Issue number5
DOIs
StatePublished - Mar 2005
Externally publishedYes

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Drug Monitoring
Hematopoietic Stem Cells
Transplants
Aspartic Acid
Alkaline Phosphatase
Transplant Recipients
Voriconazole
Mycoses
Antifungal Agents
Physiologic Monitoring
Genetic Polymorphisms
Aspergillus
Alanine Transaminase
Bilirubin
Pharmaceutical Preparations
Cytochrome P-450 Enzyme System
Isoenzymes
Liver Diseases
Creatinine
High Pressure Liquid Chromatography

Keywords

  • Hepatotoxicity
  • Therapeutic drug monitoring
  • Voriconazole

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Voriconazole therapeutic drug monitoring in allogeneic hematopoietic stem cell transplant recipients. / Trifilio, S.; Ortiz, R.; Pennick, G.; Verma, Amit K.; Pi, J.; Stosor, V.; Zembower, T.; Mehta, J.

In: Bone Marrow Transplantation, Vol. 35, No. 5, 03.2005, p. 509-513.

Research output: Contribution to journalArticle

Trifilio, S. ; Ortiz, R. ; Pennick, G. ; Verma, Amit K. ; Pi, J. ; Stosor, V. ; Zembower, T. ; Mehta, J. / Voriconazole therapeutic drug monitoring in allogeneic hematopoietic stem cell transplant recipients. In: Bone Marrow Transplantation. 2005 ; Vol. 35, No. 5. pp. 509-513.
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