Population pharmacokinetics of subcutaneous C1-inhibitor for prevention of attacks in patients with hereditary angioedema

Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology
Dipti PawaskarJagdev Sidhu

Abstract

Long-term prophylaxis with subcutaneous (SC) administration of a highly concentrated plasma-derived C1-esterase inhibitor (C1-INH) formulation was recently approved by the Food and Drug Administration for hereditary angioedema (HAE) attack prevention. To characterize the population pharmacokinetics of C1-INH (SC) (HAEGARDA® ; CSL Behring) in healthy volunteers and HAE patients, and assess the variability and influence of covariates on pharmacokinetics. C1-INH functional activity data obtained after administration of various C1-INH (intravenous; IV) and C1-INH (SC) doses from 1 study in healthy volunteers (n = 16) and 2 studies in subjects with HAE (n = 108) were pooled to develop a population pharmacokinetic model (NONMEM v7.2). Pharmacokinetic parameters derived from steady-state simulations based on the final model were also evaluated. C1-INH functional activity following C1-INH (SC) administration was described by a linear one-compartment model with first-order absorption and elimination, with inter-individual variability in all parameters tested. The mean population bioavailability of C1-INH (SC), and pharmacokinetic parameters for clearance (CL), volume of distribution, and absorption rate were estimated to be ~43%, 1.03 m...Continue Reading

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Citations

Mar 27, 2019·Expert Opinion on Biological Therapy·Francesca PeregoMarco Cicardi
Apr 3, 2020·Expert Review of Clinical Immunology·Maria Fernanda Villavicencio, Timothy Craig
Mar 23, 2019·Allergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology·Jonathan A BernsteinMoshe Fridman
Jun 10, 2020·Allergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology·Donald LevySubhransu Prusty
Apr 18, 2021·Clinics and Research in Hepatology and Gastroenterology·Nayla MumnehMarie Borum
Oct 28, 2019·The Journal of Allergy and Clinical Immunology. in Practice·Allen P KaplanJoseph Chiao

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