title: Subcutaneous injection of factor IX for the treatment of haemophilia B.
abstract: Haemophilia B patients are normally treated, either prophylactically or in response to bleeding episodes, by frequent intravenous injections of factor IX purified from blood donors. Here we show in model animal experiments that purified human factor IX, when injected subcutaneously, is rapidly (in 3-11 h) and reasonably efficiently (30-40% of an equivalent intravenous dose) transported at least partly by the lymphatic drainage of the skin into the bloodstream, mostly in a biologically active form. This suggests that patients could be treated prophylactically by subcutaneous rather than intravenous injection, where the short delay in raising plasma factor IX to haemostatic levels would be clinically acceptable. More generally, our studies emphasize that the subcutaneous route of injection should be useful for other therapeutic proteins, including other clotting factors, which have to be delivered to the bloodstream, as long as their half-life is at least a few hours allowing time for transport into the general circulation.
authors.affiliation: Chemical Pathology Unit, Sir William Dunn School of Pathology, University of Oxford.
authors.forename: A J
authors.initials: AJ
authors.lastname: Gerrard
authors.forename: D E
authors.initials: DE
authors.lastname: Austen
authors.forename: G G
authors.initials: GG
authors.lastname: Brownlee
mesh_terms: D000818:Animals; D005164:Factor IX / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006207:Half-Life; D002836:Hemophilia B / Q000188:drug therapy / Q000378:metabolism*; D007279:Injections, Subcutaneous; D008208:Lymphatic System / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D005164:Factor IX