Improvement Of Pharmacokinetic, Pharmacodynamic And Thrombopoietic Activities Of Human Interleukin-11 Mutein By Pegylation.

e19574 Background: Chemical modification of recombinant human interleukin-11 (rhIL-11) by polyethylene glycol improved the pharmacokinetics (PK), but not remaining biological activity. Human interleukin-11 mutein (mIL-11) has been shown the improved safety and equivalent efficacy at one-third of the clinical dose of rhIL-11 in chemotherapy-induced thrombocytopenia (CIT) patients. Methods: To evaluate whether PEGylated mIL-11 (PEG-mIL-11) could reduce the toxicity and the frequency of administration without compromising biological activities, comparative preclinical studies on PEG-mIL-11 and mIL-11 in normal and myelosuppressed animals were performed. Results: In vitro biological assay showed that the ED50 value of purified mono-PEG-mIL11 was comparable to that of mIL-11. The PK parameters such as AUC of PEG-mIL-11 were at least 4-fold larger than those of mIL-11 at the same dosage. The thrombopoietic activity resulting from a single PEG-mIL-11 administration was almost similar to that achieved from multip...