Preclinical Pharmacokinetics Of Polyethylene Glycolylated Recombinant Human Interleukin-6 (PEG-rhIL-6)

Interleukin 6 (IL-6) is one of cytokines cytokine with pleiotropic functions and is produced by a variety of cell types. It has regulatory effects on the immune, hematopoietic , digestive , endocrine and nervous systems. Up to now, recombinant IL-6 has come into phase III clinical studies overseas, and it has been ranked as developed emphases and come into preclinical studies in China. IL-6 is a candidate drug that may prevent the thrombocytopenia caused by chemotherapy and irradiation therapy. The stability of IL-6 in vivo is poor because of proteolysis .The half-life of IL-6 is short because of. rapid renal excretion and broad systemic distribution. Therefore, to achieve a sufficient increasement in peripheral platelet numbers, very high dosage and frequent administration of IL-6 are required. This causes unexpected side-effects, including pyrexia, acute-phase reactions and anorexia.Some studies indicated that chemical modification of bioactive proteins and peptides with water soluble polymeric modifiers, typified by polyethylene glycol (PEG), could overcome these side-effects. Chemical modification of IL-6 with PEG, effectively prolong half-life by increasing its molecular size, resistance to proteases and decreasing renal excretion rate and production of antibody.This could enhance its desirable thrombopoietic effect and reduce undesirable effects in vivo. Recently, PEG-rhIL-6 was newly developed by institute of China and is going to be used as a thrombopoietic agent.. In order to study the pharmacokinetics, illustrate pharmacokinetic features, establish model ,support pharmacokinetic study in human and offer the reference for clinical study, the pharmacokinetics,distribution and excretion of PEG-rhIL-6 in rats were studied by ¹²⁵I isotope tracing method. The results are as follows:...