• Jai N Patel, Issam S Hamadeh, Myra Robinson, Zainab Shahid, James Symanowski, Nury Steuerwald, Alicia Hamilton, Emily S Reese, Dragos C Plesca, Justin Arnall, Margaret Taylor, Jigar Trivedi, Michael R Grunwald, Jonathan Gerber, Nilanjan Ghosh, Belinda Avalos, and Edward Copelan.
• Department of Cancer Pharmacology, Levine Cancer Institute, Atrium Health, Charlotte, North Carolina, USA.
• Clin. Pharmacol. Ther. 2020 Mar 1; 107 (3): 571-579.

AbstractThere is a high risk of voriconazole failure in those with subtherapeutic drug concentrations, which is more common in CYP2C19 (cytochrome P450 2C19) rapid/ultrarapid metabolizers (RMs/UMs). We evaluated CYP2C19 genotype-guided voriconazole dosing on drug concentrations and clinical outcomes in adult allogeneic hematopoietic cell transplant recipients. Poor (PMs), intermediate (IMs), and normal metabolizers (NMs) received voriconazole 200 mg twice daily; RMs/UMs received 300 mg twice daily. Steady-state trough concentrations were obtained after 5 days, targeting 1.0-5.5 mg/L. Of 89 evaluable patients, 29% had subtherapeutic concentrations compared with 50% in historical controls (P < 0.001). Zero, 26%, 50%, and 16% of PMs, IMs, NMs, and RMs/UMs were subtherapeutic. Voriconazole success rate was 78% compared with 54% in historical controls (P < 0.001). No patients experienced an invasive fungal infection (IFI). Genotype-guided dosing resulted in $4,700 estimated per patient savings as compared with simulated controls. CYP2C19 genotype-guided voriconazole dosing reduced subtherapeutic drug concentrations and effectively prevented IFIs.© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.

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