Software for Dosage Individualization of Voriconazole: a Prospective Clinical Study [Clinical Therapeutics]

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.

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