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

The purpose of this study is to investigate the pharmacokinetics and safety 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.

• Drug: Fluconazole Loading Dose
  Single Fluconazole loading dose 25 mg/kg
  Other Name: Diflucan
• Drug: Fluconazole Loading Dose & High Dose
  Fluconazole loading dose 25 mg/kg, followed by fluconazole 12 mg/kg q24 hours for total of 5 days
  Other Name: Diflucan

• Loading Dose
  Loading Dose
  Intervention: Drug: Fluconazole Loading Dose
• Loading & high dose
  Loading dose & high dose Fluconazole
  Intervention: Drug: Fluconazole Loading Dose & High Dose

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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