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.
Sturgill
M G
MG
College of Pharmacy, Rutgers, State University of New Jersey, Piscataway, 08854-8020, USA.
Rashidbaigi
A
A
Liao
M J
MJ
Zhao
X X
XX
Hua
J
J
Trout
R
R
Knill
J R
JR
Grasing
K W
KW
D015088:2',5'-Oligoadenylate Synthetase / Q000097:blood*; D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged
D016898:Interferon-alpha; D015088:2',5'-Oligoadenylate Synthetase