Software for Dosage Individualization of Voriconazole: a Prospective Clinical Study

William Hope, Gary Johnstone, Silvia Cicconi, Timothy Felton, Joanne Goodwin, Sarah Whalley, Anahi Santoyo-Castelazo, Virginia Ramos-Martin, Jodi Lestner, Leah Credidio, Aaron Dane, Daniel F Carr, Munir Pirmohamed, Rahim Salim, Michael Neely

Research output: Contribution to journalArticlepeer-review

Abstract

Voriconazole is a first-line antifungal agent. Therapeutic drug monitoring is a standard of care. The best way to adjust dosages to achieve desired drug exposure endpoints is unclear due to nonlinear and variable pharmacokinetics. Previously described software was used to prospectively adjust voriconazole dosages. CYP2C19 and CYP3A4 and CYP3A5 genotype was determined. The primary endpoint was the proportion of patients with a Cmin at 120 hours in the range 1-3 mg/L using software to adjust voriconazole dosages. A total of 19 patients were enrolled and 14 were evaluable. Of these, 12/14 (85.7%, 95% CI 57.2 - 98.2%) had a Cmin at 120 hours post-treatment initiation of 1-3 mg/L, which was higher than the a priori expected proportion of 33%. There was no association of CYP genotype-derived metaboliser phenotype with voriconazole AUC. Software can be used to adjust the dosages of voriconazole to achieve drug exposures that are safe and effective.

Original languageEnglish
JournalAntimicrobial Agents and Chemotherapy
Early online date22 Jan 2019
DOIs
Publication statusPublished - 2019

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