Extravascular administration of interferon alfa-n3 increases serum exposure and 2-5(A) synthetase activity

The objective of this study was to evaluate the pharmacokinetics, pharmacod ynamic response, and safety of single intravenous (IV), intramuscular (IM), and subcutaneous (SQ) doses of interferon alfa-n3. Six healthy adults rece ived 10 million units of IV: IM, and SQ intelferon alfa-n3 in a randomized three-period crossover fashion. Serum interferon alfa-n3 concentrations and 2'-5'-oligoadenylate synthetase (2-5[A] synthetase) activity in peripheral blood mononuclear cells were determined after each dose. Extravascular adm inistration significantly increased mean serum interferon alfa-n3 AUC value s (1152 +/- 214, 944 +/- 209, and 576 +/- 188 U.h/mL, p < 0.001, with SQ, I M, and IV administration, respectively) and 2-5(A) synthetase activity at 3 6 and 48 hours after dosing. Mild to moderate flu-like symptoms were report ed by all 6 subjects, with no route-related difference in type or incidence . Interferon alfa-n3 is generally well tolerated by the IV, IM, and SQ rout es, with IM and SQ administration maximizing serum exposure and 2-5(A) synt hetase activity.