Background: The optimal timing for therapeutic drug monitoring (TDM) of voriconazole in Asians, who have higher rates of poor metabolisers than non-Asians, is unclear. This can cause unexpectedly high concentrations and delays in reaching steady-state levels.
Objectives: To determine the appropriate timing of TDM in Japanese patients receiving voriconazole.
Patients/methods: Trough levels (Cmin ) were measured on days 3-5 (recommended timing, RT) and days 6-14 (delayed timing, DT) after starting voriconazole in patients receiving an appropriate dosage. Considering bioavailability, Cmin was only compared in patients receiving oral voriconazole.
Results: A total of 289 and 186 patients were included in the safety and pharmacokinetic analyses, respectively. There was a significant difference in Cmin measured no later than and after day 5 (3.59 ± 2.12 [RT] vs. 4.77 ± 3.88 μg/mL [DT], p = .023), whereas no significant difference was observed on cutoff day 6 (3.91 ± 2.60 vs. 4.40 ± 3.94 μg/mL, p = .465), suggesting that Cmin close to the steady-state was achieved after day 5. DT causes a delay in achieving the therapeutic range. The hepatotoxicity rates were 21.5% and 36.8% in the RT and DT groups, respectively (p = .004); DT was an independent risk factor for hepatotoxicity.
Conclusion: Although steady-state concentrations may not be achieved by day 5, early dose optimisation using RT can prevent hepatotoxicity in Japanese patients. TDM should be performed on days 3-5 to ensure safety. However, subsequent TDM may be necessary due to a possible further increase in Cmin .
Keywords: antifungal; hepatotoxicity; therapeutic drug monitoring; timing; visual symptom; voriconazole.
© 2023 The Authors. Mycoses published by Wiley-VCH GmbH.