Population Pharmacokinetics of Sirolimus in Pediatric Patients With Neurofibromatosis Type 1

Abstract

Sirolimus clearance in children with NF1 is comparable with that in pediatric transplant patients. Clearance was most associated with body size parameters (BSA and total body weight) in children with NF1. When normalized for size, an age effect on clearance was observed in the youngest patients, most likely because of the maturational changes in drug absorption and metabolism. A mean dose of 2.0 mg/m twice a day was required for attainment of target trough concentrations of 10-15 ng/mL in children greater than 3 years of age who have NF1. The updated model will allow PK-guided individualized dosing of sirolimus in patients with NF1.