Software for Dosage Individualization of Voriconazole: a Prospective Clinical Study

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. The <i>CYP2C19</i>, <i>CYP3A4</i>, and <i>CYP3A5</i> genotypes were determined. The primary endpoint was the proportion of patients with a <i>C</i>_min at 120 h in the range 1 to 3 mg/liter using software to adjust voriconazole dosages. A total of 19 patients were enrolled, and 14 were evaluable. Of these, 12/14 (85.7%; 95% confidence interval = 57.2 to 98.2%) had a <i>C</i>_min at 120 h posttreatment initiation of 1 to 3 mg/liter, which was higher than the <i>a priori</i> expected proportion of 33%. There was no association of <i>CYP</i> genotype-derived metabolizer phenotype with voriconazole AUC. Software can be used to adjust the dosages of voriconazole to achieve drug exposures that are safe and effective. (The clinical trial discussed in this paper has been registered in the European Clinical Trials Database under EudraCT no. 2013-0025878-34 and in the ISRCTN registry under no. ISRCTN83902726.).