Subcutaneous infusion of human C1 inhibitor in swine.
Hereditary angioedema afflicts patients with unpredictable episodes of swelling that can be life threatening. Treatments approved by the Food and Drug Administration for routine prophylaxis include danazol given orally and the nanofiltered human C1 esterase inhibitor, CINRYZE, which is approved for intravenous administration. Approved for the treatment of acute attacks are the C1 esterase inhibitor, Berinert, given intravenously, and the kallikrein inhibitor, KALBITOR, given subcutaneously. C1 inhibitor has generally been non-toxic and neither pro-inflammatory nor pro-fibrotic, suggesting that it may be suitable for subcutaneous infusion. The current study used a swine model to compare blood levels of human C1 inhibitor following intravenous and subcutaneous infusion, and the effect of infusion route on heart and skin pathology. Levels of C1 inhibitor achieved with SC infusion compared favorably with levels achieved after IV infusion and were relatively more stable than those after IV infusion. Neither cardiac nor skin toxicity was observed.
Jiang
Haixiang
H
Department of Pediatrics, Duke University School of Medicine, DUMC 2611, Durham, NC 27710, USA.
Zhang
Hua-Mei
HM
Frank
Michael M
MM
D054179:Angioedemas, Hereditary / Q000188:drug therapy / Q000276:immunology; D000818:Animals; D003174:Complement C1 Inactivator Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D050718:Complement C1 Inhibitor Protein; D004797:Enzyme-Linked Immunosorbent Assay; D006321:Heart / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D055104:Infusions, Subcutaneous; D023421:Models, Animal; D012867:Skin / Q000187:drug effects; D013552:Swine
D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; C469952:SERPING1 protein, human