4CPS-078 The role of administration route in achieving therapeutic voriconazole plasma levels

<h3>Background and Importance</h3> Voriconazole, used for severe fungal infections, can be administered orally or intravenously (IV). The choice of route may impact plasma concentrations, critical for balancing therapeutic efficacy and avoiding toxicity. Comparative data on pharmacokinetic outcomes between oral and IV administration remain limited. <h3>Aim and Objectives</h3> To compare plasma concentrations of voriconazole between oral and IV routes and to assess the factors influencing the likelihood of achieving suboptimal, therapeutic, and toxic levels. <h3>Material and Methods</h3> Retrospective observational study including patients who received voriconazole between May 2021 and October 2024. Data were extracted from electronic medical records. Variables: Age. Gender. Voriconazole: Administration route. Dose. Plasmatic levels. Concentration ranges: suboptimal (&lt;1 μg/ml), therapeutic (1–5.5) and toxic (&gt;5). Body mass index (BMI). Enteral nutrition (EN). Omeprazole intake. Statistics: Spearman correlation. Chi-squared test. Mann-Whitney U. Multinomial logistic regression. The analysis was performed using SPSSv29.0. <h3>Results</h3> A total of 126 patients were included: 61 were in the IV group and 65 in the oral group.The mean age was similar: 63 ± 15 years for IV and 64 ± 15 years for oral. Men comprised 65.6% of the IV group and 66.2% of the oral. 16 patients (12.7%) reached suboptimal levels, 86 (68.3%) were in the therapeutic range and 24 (19.0%) had toxic levels. The plasma concentration was significantly higher in the IV group (U=1560.00, p=0.039). A higher percentage of patients in the IV group had toxic levels (29.5% vs. 9.2%), while the proportion of therapeutic levels was higher for oral (73.8% vs. 62.3%; χ²=9.295, p=0.009). Age (rho=0.252, p=0.004) and male sex (U=1344.00, p=0.023) were associated with higher levels. Dose, omeprazole intake, BMI and EN showed no differences. The logistic regression model based on the route of administration (including age and sex) was significant (Nagelkerke R²=0.214, p&amp;lt;0.001), with the IV route being less likely than oral to result in suboptimal (OR=0.125, p=0.006) or therapeutic levels (OR=0.232, p=0.006). <h3>Conclusion and Relevance</h3> IV voriconazole results in higher plasma concentrations and an increased risk of toxicity compared to oral administration. Age and male sex are significant factors affecting levels. Careful monitoring is advised, especially in older and male patients receiving IV therapy. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest