title: Preclinical safety evaluation of recombinant human interleukin-10.
abstract: Escherichia coli-derived recombinant human interleukin-10 (rhuIL-10) has been evaluated in an extensive series of in vivo and in vitro nonclinical safety studies, including genetic toxicology, single- and repeat-dose systemic toxicity and toxicokinetics, reproductive toxicity, and specialized irritation studies. The primary test species in the toxicology studies were the mouse and monkey based on rhuIL-10 activity in receptor binding and ex vivo cytokine assays. Supported by a detailed preclinical program of therapeutic and prophylactic animal models in autoimmune diseases, the initial clinical development program has focused on investigating the therapeutic potential of rhuIL-10 (Tenovil) in Crohn's disease and rheumatoid arthritis. The results of the subcutaneous toxicity studies, up to 3 months dosing duration in mice and 6 months dosing duration in monkeys, support the development of rhuIL-10 for present and future clinical indications by the subcutaneous route of administration.
authors.affiliation: Safety Evaluation Center, Schering-Plough Research Institute, Lafayette, New Jersey 07848, USA.
authors.forename: I Y
authors.initials: IY
authors.lastname: Rosenblum
authors.forename: R C
authors.initials: RC
authors.lastname: Johnson
authors.forename: T J
authors.initials: TJ
authors.lastname: Schmahai
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D000882:Haplorhini; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D016753:Interleukin-10 / Q000493:pharmacokinetics / Q000592:standards / Q000633:toxicity*; D051379:Mice; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000592:standards / Q000633:toxicity*; D012449:Safety; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D011994:Recombinant Proteins; D016753:Interleukin-10