Nagy J, Kapás M
Department of Pharmacokinetics and Drug Metabolism, Chemical Works of Gedeon Richter Ltd., Budapest, Hungary.
Acta Physiol Hung. 1995;83(1):31-7.
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.
TP4（精氨酸-赖氨酸-天冬氨酸-缬氨酸）是吉东·里奇特有限公司化学工厂合成的一种免疫调节四肽。本研究的目的是给出在两种TP4浓度下不同物种血浆中14C-TP4体外降解的比较数据，以便将临床前数据适当地外推至人体系统。结果表明，在每种血浆中降解都非常快，并且因所研究的物种和浓度而异。在大鼠、狗和人血浆中，初始浓度为80微克/毫升和800微克/毫升时，表观半衰期值分别为1.4、1.8、2.7分钟和3.9、6.3、13.6分钟。最易断裂的位点是精氨酸和赖氨酸之间的肽键。TP4降解与精氨酸形成之间的相关性通过一条直线得以证明，相关系数为0.99565，斜率接近-1。
