A Pharmacokinetic Study of Pediatric Micafungin Prophylaxis

Disseminated fungal infection is a major cause of morbidity and mortality in
immunocompromised children. Many of the drugs used for fungal prophylaxis have been
associated with renal and hepatic toxicity. Also, breakthrough infections have been reported
with the use of some of the oral agents due to poor oral absorption. An alternative approach
is the use of intravenous micafungin for fungal prophylaxis. Micafungin has a distinct
advantage due to its better safety profile, specifically in terms of hepatic and renal
toxicity. Currently, children who receive micafungin are given daily or alternate day dosing
(based on their last Pk study, Mehta et al 2010). The investigators objective is to examine
the pharmacokinetics of micafungin when it is given on a less frequent schedule. The
investigators hypothesize that a single dose of micafungin (at 5mg/kg) every 4 days will
provide drug exposure equivalent to daily dosing (at 1mg/kg) while reducing administration
costs and improving patient convenience (with essentially twice a week dosing regimen). Both
animal and adult data support the use of this approach. Fifteen patients will be enrolled on
this study and will be given a SINGLE DOSE of micafungin antifungal prophylaxis (5 mg/kg).
Blood samples will be drawn for pharmacokinetic measurements after administration of
micafungin. Plasma concentration data will be analyzed by compartmental and non-compartmental
pharmacokinetic analysis. The data will also be analyzed by a population pharmacokinetic
approach.

Inclusion Criteria:

- Patients who are at risk for fungal infection and require prophylaxis. Example:
patients undergoing blood and marrow transplant, immunodeficiency patients, patients
with aplastic anemia.

- Age >= 6 months to <= 10 years (at time of enrollment).

- Patients with adequate organ function (documented within 2 weeks prior to start of
micafungin):

- Creatinine < 2 times upper limit normal

- Total bilirubin and AST < 3 times upper limit normal

Exclusion Criteria:

- Patients who have history of past or evidence of active fungal disease (by either
radiological studies or biopsy proven) or are being treated for presumed fungal
infection.

- Patients who have history of allergy to micafungin or other echinocandin preparations,
such as Caspofungin or Anidulafungin.

- Patients who have received micafungin or other echinocandin preparations in the
previous two weeks.

- Patients receiving antifungal prophylaxis other than Fluconazole at the time of
enrollment. This is due to the fact that during transplant, Fluconazole is usually
switched to agents with better coverage. This will avoid the possibility of reducing
effective antifungal coverage for the purpose of the study.

- Failure to sign informed consent, or inability to undergo informed consent process.

- It is not medically advisable to obtain the specimens necessary for this study.