Voriconazole Pharmacokinetics in Children With Gastrointestinal Graft Versus Host Disease

Disseminated fungal infections are a leading cause of mortality in children who receive
hematopoietic stem cell transplantation (SCT). Therefore, children routinely receive
prophylactic and empirical antifungal therapy after SCT. The most commonly used antifungal
agent in this population is voriconazole. Voriconazole can be given via intravenous or oral
routes and children who are post SCT are routinely switched from the intravenous to oral
formulation at the time of hospital discharge. However, the absorption and systemic exposure
of oral voriconazole has not been well-described in children. Furthermore, many children who
undergo transplantation develop gastrointestinal graft versus host disease and this likely
impacts oral absorption. The magnitude of effect resulting from graft versus host disease on
absorption of voriconazole and subsequent blood concentrations in children is unknown. Thus
children with graft versus host disease are at a particularly high risk of inadequate
absorption with subsequent sub-therapeutic levels of voriconazole. They may need higher or
more frequent dosing to achieve therapeutic levels. The purpose of my research project is to
define the pharmacokinetics of oral voriconazole and establish dosing guidelines in children
following SCT.

Inclusion Criteria:

- Age ≤ 18 years, sufficient venous access to permit administration of voriconazole,
ability to take oral medications, written informed consent provided by the parent or
legally authorized representative, and Grade II or higher (extensive) gastrointestinal
graft versus host disease for those patients in the graft versus host disease patient
subset.

Exclusion Criteria:

- History of anaphylaxis attributed to voriconazole or other triazole compounds, any
concomitant condition, which in the opinion of the investigator would preclude a
patient's participation in the study, or previous participation in this study.