Pharmacokinetics and absolute bioavailability of voriconazole administred through a nasogastric tube with continuous enteral feeding to critically ill ventillated patients

Christophe Padoin, Philippe Karoubi, Antoine Rabbat, Christophe Huang, Johanna Oziel, Guillaume Van Der Meersch, Yacine Tandjaoui-Lambiotte, Frederic Gonzalez, Christophe Clech, Yves Cohen


Background: The use of nasogatric tube (NG) is one means of administering antifungal therapy to critically ill patients unable to receive medication via the oral route. The aim of the study was to determine pharmacokinetics and absolute bioavailability of voriconazole in critically ill patients receiving continuous enteral feeding.

Material/methods: A prospective multicentric, cross-over study was conducted. Stable critically ill patients on mechanical ventilation and receiving continous enteral feeding with suspected or proven fungal invasive infection (IFI) treated with voriconazole were included. Voriconazole loading dose (6mg/kg) every 12 hours for 2 doses intravenously was followed by maintenance dose of 4 mg/kg every 12 hours during 3 days. From day 4, administration of 5 mg/kg every 12h was performed through the NT. NG dose was 1 mg/kg greater than the recommended dose in order to avoid food reduction bioavailability Blood samples were collected after the fifth intravenous (IV) infusion and after the fifth NG administration. Demographic, biologic data and concomitant drugs were collected. AUC/Dose NG was compared to AUC/Dose IV using a paired T-test.

Results: 8 patients (5 males, 3 females) were evaluable. Median (range) age and bodyweight were 67.5 (49-86) years and 76.5 (57.3-117) kg. Only one patient didn’t receive esomeprazole. None had hepatic disease. Voriconazole concentrations were measured by using a validated high-performance liquid chromatographic assay. AUC/Dose were not different between route (p=0.6). Mean Voriconazole absolute bioavailabiliity was 106% and range from 77 to 135%. All subjects completed the study without any adverse effects

Conclusions: In tube-fed ventilated critically patients, a switch to NG voriconazole after initial IV therapy to simplify the treatment of IFI could be used. Furthermore, it suggests that concurrent enteral feeding does not interfere with the absorption of voriconazole and, thus, does not have to be interrupted during voriconazole administration. All trough concentration patients were superior to the efficacy target (2mg/L). However, after 6 days of treatment, 4 patients had trough concentration superior to upper therapeutic range target 5 mg/L. Therapeutic drug monitoring should be performed to avoid supratherapeutic concentration and potential neurotoxicity.




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26th European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 26th (2016)