The guideline pointed out that voriconazole AUC/MIC, trough concentration/MIC ratio are related to the efficacy of voriconazole, the maximum efficacy can be reached when the trough concentration/MIC ratio of 2~5, the trough concentration can predict the efficacy and safety: monitoring the trough concentration is more convenient and feasible than the AUC; do not recommend routine monitoring of the peak concentration to predict the clinical efficacy. Therefore, when monitoring voriconazole blood concentration, it is recommended to monitor the steady state trough concentration.

Specimens for blood concentration monitoring should be collected within 30 min after the drug has reached steady state and before the next dose. When voriconazole is given as a loading dose, steady-state concentrations can be reached on day 3, while unloaded doses require 4-7 days to reach steady-state concentrations; therefore, it is recommended that the first monitoring time should not be earlier than the fifth dose (day 3) when a loading dose is given. The target concentrations, sampling times, and assay techniques recommended by the guidelines are shown in Table 3.

If a conventional dose of voriconazole is given, only 49% (29/59) of the patients reach the blood level, which is a low rate of achievement. Therefore, it is important to both give a loading dose to bring blood concentrations to a rapid steady state and to individualize the design of a rational initial dosing regimen that takes into account the patient's age and incorporates factors such as drug-drug interactions. Children receiving voriconazole at 3 mg/kg or 4 mg/kg every 12 h show a linear clearance relationship, so to achieve blood levels in children similar to those in adults, the dose of voriconazole needs to be increased to ensure optimal blood levels and efficacy in pediatric patients. The initial dosing regimens for adults and children are shown in Table 4.

Monitor steady-state trough concentrations after administration of the above regimen and subsequently adjust the dosing regimen based on the results. If the blood concentration monitoring results are not within the target range, the patient's medication compliance needs to be checked, the voriconazole dose needs to be adjusted, and concomitant medications with interactions need to be discontinued if necessary. The voriconazole dose was increased by 50% if the steady-state blood concentration test value was below the lower limit of the target concentration range (increased to 6 mg/kg administered every 12 h for intravenous administration in adults, and increased from 200 mg administered every 12 h to 300 mg administered every 12 h for oral administration), and the dose was reduced by 25% if the test value was above the upper limit of the target concentration range, and by 25% if the test value was above 10 μg/ mL or adverse events (e.g., hepatotoxicity, psychiatric/neurotoxicity:visual disturbances), one dose was discontinued, followed by a 50% reduction in the maintenance dose. Re-monitoring of voriconazole trough concentration levels after 2 to 5 days is recommended when adjusting voriconazole dose, sequential oral administration from a vein, or when adding or discontinuing drugs that affect voriconazole.

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