Bioavailability of fluconazole administered via a feeding tube in intensive care unit patients

Abstract

Fluconazole, a triazole compound with potent activity against many medically important fungi, undergoes rapid oral absorption, and has been shown in healthy volunteers to exhibit virtually complete bioavailability. The purpose of this study is to evaluate the bioavailability of fluconazole administered via a feeding tube with concomitant enteral feeds in intensive care unit patients. Once prescribed by the attending physician, fluconazole was administered either as an intravenous infusion over 1 h or the tablet was crushed and given via a feeding tube with concomitant enteral feeds. Once blood samples were obtained (not before the fifth dose) of the first regimen, the patient could be switched over to the alternate route and blood samples were again obtained after at least five doses. All patients had normal gastrointestinal motility, normal renal, and hepatic function. Serum concentrations were determined by a validated HPLC method. The area under concentration-time curve (AUC) was calculated using the trapezoidal rule; bioavailability was determined from the ratio of AUC(tube)/AUC(intravenous). The bioavailability for five patients was calculated to be 97.2 +/- 9.8%. Fluconazole retained excellent bioavailability when crushed and administered via a feeding tube with or without concomitant enteral feeding in critically ill patients. This alternative route of administration promotes cost savings and decreases the chance for secondary infection from indwelling intravenous catheters.

Pharmacokinetics of Posaconazole Administered Orally or by Nasogastric Tube in Healthy Volunteers

“…Several published reports discuss the use of nasogastric and other types of enteral feeding tubes to administer azole antifungals, including fluconazole (1,14,19), itraconazole (15), and voriconazole (7,12,13).…”

Therapeutic concerns when oral medications are administered nasogastrically

“…NGT dosing has been shown to offer cost-savings and to decrease the risk of secondary infection from indwelling intravenous catheters in some cases. 11,12 NGT administration of voriconazole can be an alternative to i.v. treatment of suspected or documented fungal infections in mechanically ventilated patients by simplifying the treatment and reducing its cost.…”

Pharmacokinetics of sequential intravenous and enteral fluconazole in critically ill surgical patients with invasive mycoses and compromised gastro-intestinal function

“…The latter can simplify drug administration and reduce costs significantly. Nicolau et al demonstrated excellent bioavailability of fluconazole administered via a feeding tube in critically ill patients without recent gastro-intestinal (GI) surgery and normal renal and hepatic function [8]. Rosemurgy et al found a bioavailability of 77 % after a single dose of 100 mg in four patients with recent GI surgery [9].…”