Bioavailability of fluconazole in surgical intensive care unit patients: A study comparing routes of administration

Objective: Anticandidal therapy is commonly used in the surgical intensive care unit (SICU). Unfortunately, it is expensive because it is generally given intravenously, as acute trauma and abdominal surgery are often accompanied by impaired gastrointestinal function. We compared the systemic availability of fluconazole given enterally or intravenously in trauma and surgery SICU patients to determine the reliability of enteral administration. Methods: Nine adult trauma (Injury Severity Score (≥ 18) and nine adult abdominal surgery SICU patients were randomized to receive fluconazole 100 mg via the intravenous (IV) or enteral route. Patients with a bilirubin > 4.0 mg/dL or creatinine clearance < 60 mL/min were excluded. Enteral fluconazole was crushed, dissolved, and flushed through a nasogastric or feeding tube. Eleven serial blood samples were drawn over 72 hours. Area under the curve (AUC), elimination rate constant(Ke), and terminal half-life (T 1/2 ) were determined and compared (t test). Relative bioavailability was estimated (AUC(enteral)/AUC(IV)). Results: Peak concentrations occurred within 2 hours after enteral dosing and 15 minutes after IV dosing. The relative bioavailability was 77%. Weight, AUC, Ke, and T 1/2 did not differ between enteral and IV dosing. Conclusions: Fluconazole is significantly absorbed when crushed, dissolved, and given via a nasogastric or feeding tube in SICU patients. Nonsignificant trends toward lower systemic availability with enteral administration can be overcome with slightly higher doses. Since enteral administration of fluconazole costs 10% of fluconazole given intravenously, more liberal use of enteral administration offers tremendous savings. Such savings moderate the cost concerns of antifungal therapy.