TY - JOUR
T1 - Software for Dosage Individualization of Voriconazole
T2 - a Prospective Clinical Study
AU - Hope, William
AU - Johnstone, Gary
AU - Cicconi, Silvia
AU - Felton, Timothy
AU - Goodwin, Joanne
AU - Whalley, Sarah
AU - Santoyo-Castelazo, Anahi
AU - Ramos-Martin, Virginia
AU - Lestner, Jodi
AU - Credidio, Leah
AU - Dane, Aaron
AU - Carr, Daniel F
AU - Pirmohamed, Munir
AU - Salim, Rahim
AU - Neely, Michael
N1 - Copyright © 2019 Hope et al.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
U2 - 10.1128/AAC.02353-18
DO - 10.1128/AAC.02353-18
M3 - Article
C2 - 30670416
SN - 0066-4804
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
ER -