A-005. Safety, Tolerability and Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Pediatric Patients
Session: Poster Session: Antifungal Pharmacokinetics/Dynamics
Saturday, October 25, 2008: 12:00 AM
Room: Hall C
Background: Liposomal amphotericin B (L-AMB) is used for treatment of life-threatening mycoses in pediatric patients (pts). However, little is known about its safety, tolerability, and pharmacokinetics in this population.
Methods: L-AMB was studied in 40 immunocompromised children and adolescents in an open-label, sequential, dose-escalation, multidose pharmacokinetic study with 10 to13 pts in each of four dosage cohorts. Each cohort received daily dosages of 2.5, 5.0, 7.5 or 10 mg/kg L-AMB. Neutropenic pts between the ages of 1 and 17 years were enrolled if eligible to receive empirical antifungal therapy for persistent fever of > 96h despite antibacterial therapy or for treatment of documented invasive fungal infection. Pharmacokinetic parameters were measured as those of amphotericin B by HPLC and calculated by noncompartmental methods. Results: Mean age was 7.8 ± 5.2y. Median duration on study was 9.2d. There were 9 adverse event-related discontinuations, 4 of which were related to infusions. Infusion-related side effects occurred in 63 (11 %) of 565 infusions with 5 pts experiencing acute infusion related reactions (7.5 and 10 mg/kg dose levels). Serum creatinine increased from 0.45 ± 0.04 mg/dl to 0.63 ± 0.06 mg/dL (p=0.003) at end of therapy. At higher dosage levels of 7.5-10 mg/kg, there was a trend toward greater hypokalemia, azotemia, and infusion related dyspnea, vomiting, chills and rigors. The AUC0-24 values of L-AMB on day 1 ranged from 54.7 ± 32.9 at 2.5 mg/kg to 430 ± 566 µg•h/ml at 10.0 mg/kg, which were similar to those seen in adult pts. Clearance was not significantly changed across dosages. Conclusions: These findings indicate that L-AMB can be administered to pediatric patients at dosages similar to those of adults.
Andreas Groll, Childrens Hospital, Aziza Shad, Georgetown University Medical Center, Corina Gonzalez, Georgetown Univ Med Ctr, Donald Buell, Astellas Pharma US Inc, Ihor Bekersky, Astellas, Lauren Wood, NCI, Nita Seibel, MD, Child Natl Med Ctr, Washington, DC, Thomas Walsh, MD, FIDSA, National Cancer Institute, Bethesda, MD and  T. J. Walsh, None.