Does a Dosing Design Based on Plasma Drug Concentrations 3 Days after the Initiation of Oral Voriconazole Administration Improve Safety in Patients Receiving Oral Voriconazole?

Abstract

Voriconazole (VRCZ) is a target drug for therapeutic drug monitoring because of its complex pharmacokinetics and narrow recommended therapeutic range of 1 – 4 μg/mL in Japanese patients. Recently, blood was recommended to be drawn early after VRCZ administration to prevent adverse events. However, there is a concern that if the dose is changed based on the trough value at which the steady-state is not reached, VRCZ plasma concentrations will be outside the therapeutic range. Therefore, we implemented a dosing design based on plasma drug concentrations on day 4 after VRCZ administration and examined its usefulness.

The rates of achieving the VRCZ therapeutic range on day 4 after VRCZ administration and after the first dose change were 42.9％ and 70.0％, respectively. The number of dose changes required to reach the target therapeutic range was 0 for 28.6％, 1 for 85.8％, and 2 for 100％ cumulative doses. In addition, none of the 21 patients developed hepatic dysfunction before the plasma VRCZ concentrations reached the target therapeutic range.

These results suggest that a dosing design based on day 4 blood flow results may be effective for reaching the target therapeutic range of VRCZ early and continuing safe treatment.