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Extravascular Administration of Interferon Alfa‐N3 Increases Serum Exposure and 2–5(A) Synthetase Activity
Author(s) -
Sturgill Marc G.,
Rashidbaigi Abbas,
Liao MeiJune,
Zhao XiaoXia,
Hua Ji,
Trout Richard,
Knill James R.,
Grasing Kenneth W.
Publication year - 2000
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.2000.tb05986.x
Subject(s) - medicine , pharmacokinetics , dosing , interferon , interferon alfa , pharmacodynamics , crossover study , pharmacology , gastroenterology , alpha interferon , peripheral blood mononuclear cell , immunology , biology , pathology , in vitro , biochemistry , alternative medicine , placebo
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.