An Open Intravenous Multiple Dose, Multi-Center Study to Investigate the Pharmacokinetics, Safety and Toleration of Voriconazole in Children Aged 2-12 Years Who Require Treatment for the Prevention of Systemic Fungal Infection

The objective of this study is to evaluate the serum levels and pharmacokinetic parameters achieved following two dosage levels of voriconazole. In addition, the safety and toleration of intravenous voriconazole at two dosage levels in an immunocompromised pediatric patient population will be evaluated. Also, the plasma concentrations of the major metabolite of voriconazole (N-oxide) in these patients will be performed. The study is designed as a multi-center, open label multi-dose study of intravenous voriconazole. Intravenous voriconazole will be administered prophylactically twice daily to immunocompromised children at high risk for invasive mycoses. The patient population consists of children ages 2 years to 12 years of age; two age groups will be studied (2-<6, 6-12). Initial dosage levels will be 3mg/kg q12h and 4mg/kg q12h. The planned sample size is 24 children. For those children who do not complete the full 8 days of kinetics, a replacement patient will be added. Immunocompromised children at high risk for invasive mycoses will receive voriconazole prophylactically. Therapy will be initiated within 48 hours after completion of chemotherapy. Voriconazole therapy will continue until recovery from neutropenia. The first 12 children will initially receive a loading dose of 6mg/kg X 2 doses followed by 3mg/kg BID through day 4 of therapy. Twelve hour pharmacokinetics will be collected on day 4. Children will then receive 4mg/kg starting on the second dose of day 4 and will continue at that dosage level until recovery from neutropenia. Kinetics will again be collected at the 4mg/kg dosage level on day 8 of therapy. If the mean peak plasma concentration of voriconazole in the first 12 patients following 4mg/kg q12h dosing is less than 4,000ng/ml., the remaining 12 patients will receive voriconazole after day 4 at a dosage of 5mg/kg.