Pharmacokinetics of an extended-release human interferon alpha-2b formulation.
The in vivo half-life of human interferon alpha-2b (hIFN-alpha-2b) is relatively short, and frequent injections over prolonged periods are required for efficacy. An extended-release formulation of hIFN-alpha-2b (Depo/IFN) was created by encapsulation into a lipid-based drug-delivery system. The capture efficiency was 51% +/- 13% and the release half-life in human plasma at 37 degrees C was 16 days. The pharmacokinetics of Depo/IFN was compared with that of unencapsulated standard hIFN-alpha-2b (Std/IFN) in the peritoneal cavity of male BDF1 mice. Depo/IFN exhibited a 13-fold longer intraperitoneal (i.p.) half-life as compared with Std/IFN (20 vs 1.5 h). The release of free hIFN-alpha-2b from Depo/IFN into the peritoneal cavity was slow and protracted, with a 10-fold lower peak concentration and a 13-fold longer apparent half-life being observed in comparison with Std/IFN. The areas under the curve of free hIFN-alpha-2b in the peritoneal cavity were comparable for Depo/IFN and Std/IFN. hIFN-alpha-2b was detectable in plasma only after the i.p. administration of Std/IFN. These data suggest the possibility that Depo/IFN may be useful as an extended-release formulation of hIFN-alpha-2b.
Bonetti
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A
UCSD Cancer Center, La Jolla 92093-0812.
Kim
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S
D000818:Animals; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D006207:Half-Life; D006801:Humans; D007274:Injections, Intraperitoneal; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008051:Lipid Bilayers; D008297:Male; D051379:Mice; D011994:Recombinant Proteins
D003692:Delayed-Action Preparations; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008051:Lipid Bilayers; D011994:Recombinant Proteins