In vitro degradation of thymopoietin32-35 in human, dog and rat plasma.

TP4 (Arg-Lys-Asp-Val) is a synthetic immunomodulatory tetrapeptide of Chemical Works of Gedeon Richter Ltd. The aim of this study was to give comparative data on the in vitro degradation of 14C-TP4 in plasma of different species at two TP4 concentrations to allow suitable extrapolation of preclinical data to human system. The results show that the degradation was very fast in each plasma and varied by the species and concentrations studied. In rat, dog and human plasma for initial concentration of 80 micrograms/ml and 800 micrograms/ml the apparent half-life values proved to be 1.4, 1.8, 2.7 and 3.9, 6.3, 13.6 minutes, respectively. The most susceptible breakdown point was the peptide bond between Arg and Lys. The correlation between TP4 degradation and arginine formation was demonstrated by a straight line with a correlation coefficient of 0.99565 and a slope close to -1.