Population pharmacokinetics of recombinant human C1 esterase inhibitor in children with hereditary angioedema
| Autor: | Anurag Relan, Colm Farrell, Siobhan Hayes, John Anderson |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Pulmonary and Respiratory Medicine medicine.medical_specialty Adolescent Immunology Population Models Biological Young Adult HUMAN C1-ESTERASE INHIBITOR Pharmacokinetics Internal medicine Humans Immunology and Allergy Medicine Computer Simulation Dosing Young adult Child education Aged Volume of distribution education.field_of_study business.industry Angioedemas Hereditary Middle Aged bacterial infections and mycoses medicine.disease Recombinant Proteins Clinical trial Child Preschool Hereditary angioedema Female business Complement C1 Inhibitor Protein |
| Zdroj: | Annals of Allergy, Asthma & Immunology. 126:707-712 |
| ISSN: | 1081-1206 |
| Popis: | BACKGROUND Recombinant human C1 esterase inhibitor (rhC1-INH) is indicated in the United States for the treatment of acute hereditary angioedema (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 perform population PK modeling to predict C1-INH levels by age after by age rhC1-INH 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 and 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 An unpublished population PK model was refined and used to simulate C1-INH exposure.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 the inclusion of bodyweight in the model. Simulations of the recommended rhC1-INH dosing regimen (bodyweight |
| Databáze: | OpenAIRE |
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