The pharmacokinetic profile of dupilumab has been evaluated in studies of adults with atopic dermatitis and in those with asthma. Dupilumab demonstrated nonlinear target-mediated pharmacokinetics. Following subcutaneous injection, mean (± SD) trough dupilumab concentrations ranged from 29.2 ± 18.7 mcg/mL to 36.5 ± 22.2 mcg/mL in those receiving 200 mg every other week and from 60.3 ± 35.1 mcg/mL to 79.9 ± 41.4 mcg/mL in patients receiving 300 mg every other week. Bioavailability following subcutaneous injection ranged from 61% to 64%, with a mean volume of distribution of 4.8 ± 1.3 L. Dupilumab is degraded to smaller peptides and amino acids similar to endogenous immunoglobulins. In clinical studies, the median time to non-detectable concentrations ranged from 9 to 13 weeks.
Trough serum concentrations were evaluated in adolescents 12 to 17 years of age receiving doses of 200 mg (in those weighing less than 60 kg) or 300 mg every other week. The mean steady state trough concentration was 54.5 ± 27.0 mcg/mL, similar to the values obtained in adults. These results were replicated in the pharmacokinetic component of a phase 2a ascending-dose study. This study, also conducted by the manufacturer, evaluated dupilumab in 40 adolescents (12 to 17 years of age) with moderate-to-severe atopic dermatitis and 37 children (6 to 11 years of age) with severe disease. Patients received a single dose of 2 mg/kg or 4 mg/kg, followed by a 4-week treatment phase starting 8 weeks after the initial dose.[4,5]
Pediatr Pharm. 2019;25(6) © 2019 University of Virginia