Pharmacokinetics (PK) Study of a Fluconazole Loading Dose in Infants and Toddlers

This is an open label study to investigative the pharmacokinetics and safety of a fluconazole
loading dose in infants and toddlers < 2 years of age with suspected sepsis. There will be
two treatment groups: single fluconazole loading dose 25 mg/kg; fluconazole loading dose
25mg/kg followed by 12 mg/kg daily for total of 5 days. There will be three age cohorts
within each group: pre-term < 30 week EGA infants > 48 hours and < 31 days; > 30 weeks EGA
infants > 48 hours and < 31 days; infants ≥ 31 days and < 2 years of age. The study requires
administration of fluconazole over 1-5 days depending on treatment group followed by 1 week
of safety monitoring. Six to eight 100 µL PK samples will be obtained over the 5 days of drug
administration. The risks are reasonable vs. the benefits and have been minimized
appropriately. There may be benefit to the subjects (administration of empirical antifungal
therapy), and information from the study may benefit a large number of other infants and
toddlers with suspected or proven fungal sepsis. There is a data analysis plan.

Inclusion Criteria:

- suspected sepsis with blood culture within 48 hours

- age ≥ 48 hours and < 2 years of age

- sufficient venous access to permit study drug administration

Exclusion Criteria:

- allergic reaction to azole

- history of fluconazole administration in prior 5 days

- liver dysfunction

- renal failure

- concomitant use of cyclosporine, tacrolimus, or azithromycin