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, pharmacodynamic response, and safety of single intravenous (IV), intramuscular (IM), and subcutaneous (SQ) doses of interferon alfa-n3. Six healthy adults received 10 million units of IV, IM, and SQ interferon 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 administration significantly increased mean serum interferon alfa-n3 AUC values (1152 ± 214, 944 ± 209, and 576 ± 188 U·h/mL, p < 0.001, with SQ, IM, and IV administration, respectively) and 2–5(A) synthetase activity at 36 and 48 hours after dosing. Mild to moderate flu-like symptoms were reported 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 routes, with IM and SQ administration maximizing serum exposure and 2–5(A) synthetase activity.