Preclinical toxicity studies with two thymopoietin-like peptides.
Differentiation of T-lymphocytes is regulated by thymopoietin, a 49 amino acid polypeptide chain. The site of immunological activity is in the 32-36 (Arg-Lys-Asp-Val-Tyr) fragment. This pentapeptide can be reduced to a tetrapeptide (RGH-0206: Arg-Lys-Asp-Val) and further to a tripeptide (RGH-0205: Arg-Lys-Asp) which still retains immunological activity. To prepare Phase I and II clinical trials preclinical toxicity studies were duly performed. Mice, rats and dogs tolerated a single 1000 mg/kg dose i.v. without any symptom. In a 14-day i.v. test on Lati:Han:WISTAR rats daily doses of 10,25, 62.5, 150, 400 and 1000 mg/kg of either test compound were tolerated without symptom or damage. In a 28-day i.v. toxicity test on Wobe:BEAGLE dogs given daily doses of 6, 20 and 60 mg/kg of either test compound, no adverse reaction occurred. The low toxicity of both RGH-0205 and RGH-0206 are probably attributable to their short half-life, as half-life of the pentapeptide fraction is less than 30 sec in humans. It was concluded that the planned clinical dose of 1 mg/kg i.v. was safe for both peptides for short-term administration.
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005128:Eye Diseases / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D007674:Kidney Diseases / Q000139:chemically induced; D051379:Mice; D009422:Nervous System Diseases / Q000139:chemically induced; D009842:Oligopeptides / Q000378:metabolism / Q000633:toxicity*; D010446:Peptide Fragments; D051381:Rats; D011919:Rats, Inbred Strains; D013946:Thymopoietins
D009842:Oligopeptides; D010446:Peptide Fragments; D013946:Thymopoietins; C045801:RGH 0205; C045802:thymocartin