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 (i.v.), intramuscular (i.m.), and subcutaneous (SQ) doses of interferon alfa-n3. Six healthy adults received 10 million units of i.v., i.m., 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, i.m., and i.v. 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 i.v., i.m., and SQ routes, with i.m. and SQ administration maximizing serum exposure and 2-5(A) synthetase activity.