Voriconazole Therapeutic Drug Monitoring in Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Recipients: Significance in Patients with Abnormal Hepatic Function. Session Type: Publication Only

S. Trifilio, R. Ortiz, G. Pennick, J. Pi, A. Verma, J. Mehta

Author address: 

Northwestern University, Chicago, USA; UT Health Science Center, San Antonio, USA

Abstract: 

Voriconazole is a triazole agent with significant activity against Candida and Aspergillus. It is metabolized by the hepatic cytochrome P450 enzymes 2C19, 2C9 and 3A4. CYP2C19, which plays a significant role in the metabolism, exhibits significant genetic polymorphism. As a result, some patients metabolize the drug poorly. The clinical significance of poor metabolism and any possible increase in voriconazole levels due to it is unknown, and the utility of voriconazole therapeutic drug monitoring is unclear. We monitored steady-state trough serum voriconazole levels in 12 allogeneic hematopoietic stem cell transplant recipients using a new HPLC assay (Pennick et al. Antimicrob Agents Chemother 2003;47:2348-50). All patients had received non-myeloablative conditioning with 100 mg/m2 melphalan (+ 50 mg/kg cyclophosphamide if not prior autograft). GVHD prophylaxis comprised cyclosporine/tacrolimus with mycophenolate mofetil. Voriconazole was commenced at the dose of 200 mg twice daily orally in 10 patients, and 400 mg twice daily for a day followed by 200 mg twice daily in 2. Patients had drug levels estimated once (n=8), twice (n=2), or 3-4 times (n=1 each). The levels were checked 5-18 days (median 10) after starting the drug or modifying the dose. The intention was to achieve a level greater than 0.5-1.0 g/mL corresponding to the in vitro MIC90 of voriconazole for Aspergillus spp. The 12 baseline levels ranged from 0.3 to 6.8 g/mL (median 1.4; mean 2.1; SD 1.9). Overall, the 19 levels were 0.3-6.8 g/mL (median 1.7; mean 2.4; SD 2.2); with only 2 levels
2003

abstract No: 

5494

Full conference title: 

American Society of Hematology 45th Annual Meeting
    • ASH 45th (2003)