Pharmacokinetics of Interferon α‐2b in Healthy Volunteers

Abstract

In a three-way crossover design, 12 healthy male volunteers received 5 X 10(6) IU/m2 body surface area interferon alpha-2b(IFN alpha-2b) by intravenous (IV) infusion over 30 minutes, intramuscular (IM) injections, and subcutaneous (SC) injections. Blood and urine samples were collected at specified times, and analysis of IFN alpha-2b concentrations was performed by immunoradiometric assay. "Flulike" symptoms were the most frequently reported adverse experiences and were independent of the route of administration. After a 30-minute IV infusion, IFN alpha-2b disappeared rapidly from serum, with distribution and elimination phase half-lives of 0.1 hour and 1.7 hours, respectively. Interferon alpha-2b was absorbed slowly after IM and SC administration, with similar absorption half-lives of 5.8 and 5.5 hours, respectively. The observed maximal concentrations after IM and SC administration were 42.1 IU/mL at six hours and 45.8 IU/mL at eight hours, respectively. Interferon alpha-2b was eliminated with half-lives of 2.2 hours after IM administration and 2.9 hours after SC administration. The areas under the serum concentration-time curves for the SC and IM doses were higher than those obtained for the IV infusion. Measurable amounts of IFN alpha-2b were not found in urine regardless of the route of administration.

Alpha interferon (2b) in combination with zidovudine for the treatment of presymptomatic feline leukemia virus-induced immunodeficiency syndrome

“…The pharmacokinetics of IFN-a delivered subcutaneously to cats (half-life, 2.9 h) were similar to those recorded for humans, monkeys, and dogs, in which the elimination halflife ranged from 1.8 to 4.8 h (38,48). In contrast to other mammalian retrovirus studies in which IFN-ot has been used to inhibit de novo virus infection (3,8,42), results of this study demonstrate that IFN-ot has a significant, dose-dependent antiviral effect on persistent antigenemia.…”

“…The use of IFN-ot alone and in combination with AZT in other mammalian retrovirus infections is limited, but similar to its application for HIV infections, these agents act synergistically to prophylactically prevent murine and feline retrovirus infections (42,51). Phase I studies in humans have indicated a half-life of IFN-oa in plasma of 2 to 3 h following subcutaneous injection, with dose limitations related to pyrexia, lethargy, myalgia, and hematological toxicity (38,48). Initial clinical trials with IFN-cx against HIV-associated Kaposi sarcoma have been encouraging in terms of antiviral and antitumor responses, significant increases in CD4+ cells, and decreases in circulating viral antigen in those patients who respond to therapy (4,10,23).…”

Enhanced gene expression in mouse muscle by sustained release of plasmid DNA using PPE-EA as a carrier

“…This is a secretory protein that has a serum half-life of 1.7 h. 14 An N/P ratio of 0.5 has been selected due to its higher efficiency in the previous study. Following intramuscular injection, PPE-EA/DNA complexes generated 1.8 times higher IFN-␣2b in blood circulation than naked DNA on day 14 (P Ͻ 0.05), although at other time points, the expression levels were similar to those of naked DNA injection.…”

Continuous delivery of human type I interferons (α/β) has significant activity against acute myeloid leukemia cells in vitro and in a xenograft model

“…5 However, it remains unclear whether this lack of efficacy was related to poor antileukemic effect in vivo or a failure to maintain stable therapeutic IFN-␣ levels because of its short half-life. 6 In this study, we compare the antileukemic effects of IFN-␣ and ␤ against a variety of AML cell lines in a xenograft model. Two different schedules of administration were used: the traditional high-dose multiple bolus injection approach using recombinant IFN-␤, as well as continuous low-dose delivery, achieved here through gene transfer with adenoassociated virus (AAV) vectors.…”