Pharmacokinetic analysis of human plasma-derived pasteurized C1-inhibitor concentrate in adults and children with hereditary angioedema: a prospective study.
BACKGROUND
Hereditary angioedema (HAE) is a rare and potentially life-threatening disease presenting with acute edema of subcutaneous tissues and/or mucous membranes. Patients with HAE have abnormally low or dysfunctional C1-inhibitor (C1-INH). Preventing the progression of acute attacks is the main goal of C1-INH replacement therapy; knowledge of the C1-INH concentrate half-life is of crucial importance. This pharmacokinetic study was conducted to investigate the pharmacokinetics of pasteurized human plasma-derived C1-INH concentrate (pC1-INH).


METHODS
This was a prospective, single-center study of six children and 34 adults with an established diagnosis of HAE. On-demand treatment with pC1-INH was administered to all children, whereas adults received either pC1-INH on-demand treatment or individual replacement therapy (IRT). Functional C1-INH plasma levels were fitted to a single-compartment model with nonlinear regression, and the area under the curve was standardized to a dose equivalent of 15 U/kg body weight of pC1-INH concentrate.


RESULTS
The median half-life of functional C1-INH plasma levels in pediatric patients receiving on-demand therapy was 32.9 hours (mean, 31.5 hr). In adults, the median half-lives of functional C1-INH plasma levels after on-demand therapy were 39.1 hours (mean, 47.8 hr) and 30.9 hours (mean 33.3 hr) for patients on IRT. The median times to achieve maximum plasma activity after administration were 0.6 hour for children, 1.0 hour for adults receiving on-demand treatment, and 0.5 hour for adults on IRT.


CONCLUSIONS
pC1-INH concentrate has a long median terminal elimination half-life and rapidly reaches maximum plasma concentrations. This rapid onset of clinical efficacy is essential in patients suffering from HAE.
Martinez-Saguer
Inmaculada
I
Centre of Paediatrics III, Department of Haematology, Oncology and Haemostasis, Comprehensive Care Centre for Thrombosis and Haemostasis, Johann-Wolfgang-Goethe-University Hospital, Frankfurt am Main, Germany.
Rusicke
Eva
E
Aygören-Pürsün
Emel
E
von Hentig
Nils
N
Klingebiel
Thomas
T
Kreuz
Wolfhart
W
D000293:Adolescent; D000328:Adult; D054179:Angioedemas, Hereditary / Q000097:blood / Q000188:drug therapy*; D019540:Area Under Curve; D001835:Body Weight; D002648:Child; D003174:Complement C1 Inactivator Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D050718:Complement C1 Inhibitor Protein; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011446:Prospective Studies; D055815:Young Adult
D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; C469952:SERPING1 protein, human