Population pharmacokinetics of recombinant human C1 esterase inhibitor in children with hereditary angioedema

BackgroundRecombinant human C1 esterase inhibitor (rhC1-INH) is indicated in the United States for treatment of acute hereditary angioedema (HAE) attacks adolescents and adults; it also Europe children aged 2 years older. A need exists further insight into potential pharmacokinetic (PK) differences functional C1-INH levels by age (ie, children, adolescents, adults).ObjectiveTo perform population PK modeling to predict after rhC1-INH administration.MethodsData from a phase pediatric trial (children 4-13 at screening) were added database 6 trials adults adolescents. An unpublished model was refined used simulate exposure.ResultsAnalysis included 153 individuals (14 healthy volunteers; 139 patients with HAE) 1788 measurements (59 20 trial). Bodyweight (population weight, 16-128 kg) key predictor volume distribution. Age not inclusion bodyweight model. Simulations recommended dosing regimen (bodyweight <84 kg, 50 U/kg; ≥84 4200 U) revealed that overall exposure comparable among groups. Predicted peak concentrations or above lower level normal (≥0.7 U/mL) 99.8% (≥18 years), (14-17 96.0% (2-13 years).ConclusionThe analyses support same weight-based HAE as currently adults. These results clinical data, which similar safety efficacy profiles across these