Systemic Absorption and Activity of Recombinant Consensus Interferons After Intratracheal Instillation and Aerosol Administration

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Abstract
Purpose. The pulmonary pharmacokinetics and bioactivity of E. coli derived recombinant consensus interferon (CIFN) and a modified lactose-conjugated consensus interferon (LacCIFN) were evaluated in animals. Methods. Estimated doses of 20 and 100 µg/kg of the interferons were administered to anesthetized rats by aerosol via ultrasonic nebulizer as well as intravenous injection. Rats also received nominal doses of 50 and 200 µg/kg via intratracheal instillation (IT). Hamsters were treated with interferon via various routes including IT. The effectiveness of treatment was assessed by the resistance to development of hind leg paralysis following infection with encephalomyocarditis virus. Results. Significant amounts of CIFN and LacCIFN were found in rat plasma after aerosol administration. Peak plasma levels occurred ≈25–30 minutes with estimated bioavailabilities approaching 70%. Absorption of CIFN was rate limiting and plasma levels were detectable 12 hr post-dose. The CIFN at IT doses as low as 5 µg/kg was effective at reducing paralysis in hamsters but protection was variable and doses of up to 100 µg/kg were not 100% effective. Conclusions. Despite the incomplete protection, the results demonstrate the feasibility of treating systemic viral infections with interferon administered directly to the lungs.