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

Background Recombinant human C1 esterase inhibitor (rhC1-INH) is indicated in the United States for the treatment of acute HAE attacks in adolescents and adults; it is also indicated in Europe for children aged 2 years and older. A need exists for further insight into potential pharmacokinetic (PK) differences in functional C1-INH levels by age (ie, children, adolescents, and adults). Objective To employ population PK modeling to predict C1-INH levels following rhC1INH administration. Methods Data from a phase 2 pediatric trial (children aged 4-13 years at screening) were added to a database of 6 trials in adults/adolescents. An unpublished population PK model was refined and used to simulate C1-INH exposure. Results Analysis included 153 individuals (14 healthy volunteers; 139 patients with HAE) and 1788 functional C1-INH measurements (59 from 20 patients in the pediatric trial). Bodyweight (population weight, 16-128 kg) was a key predictor of C1-INH volume of distribution. Age was not a predictor of C1-INH PK after inclusion of bodyweight in the model. Simulations of the recommended rhC1-INH dosing regimen (bodyweight Conclusion Analyses support the same weight-based rhC1-INH dosing for HAE attacks in children as currently recommended for adolescents/adults. These results support clinical trial data, which demonstrated similar safety and efficacy profiles across these age groups.