Pharmacodynamics of biological response in vivo after single and multiple doses of interferon-beta.

摘要: Interferons (IFNs) induce gene regulation in vivo that may be used to identify effective doses, schedules, and potential correlates of therapeutic response. To critically examine minimum dose, duration response, cumulative effects repetitive a range subcutaneous doses IFN beta ser was studied 32 healthy human volunteers. IFN-induced products assessed were 2-microglobulin, neopterin, tryptophan serum 2',5'-oligoadenylate (2-5A) synthetase activity peripheral blood mononuclear cells. Eight subjects per group received 0.09, 0.9, 9, or 45 MU beta. Responses measured at 24, 48, 72 h after single multiple doses. The lowest biologically dose 0.9 MU; significant (p < 0.02) increases observed 24 2-microglobulin cellular 2-5A activity. At the two higher 9 MU, changes all 0.01). A response 0.01) over 0.09-45 for these intracellular products. Changes correlated significantly with each other. as great magnitude suggesting an alternate-day schedule would maintain biological