LAUSR

Graphical abstract Figure. No Caption available. Abstract In order to improve the pharmacokinetic and pharmacodynamic properties of recombinant human interleukin‐11 mutein (mIL‐11) and to reduce the frequency of administration, we examined the feasibility of chemical modification of mIL‐11 by methoxy polyethylene glycol succinimidyl carbonate (mPEG‐SC). PEG‐mIL‐11 was prepared by a pH controlled amine specific method. Bioactivity of the protein was determined in a IL‐11‐dependent in vitro bioassay, its pharmacodynamic and pharmacokinetic properties were investigated by using normal and thrombocytopenic monkey models. N‐terminus sequencing and peptide mapping analysis revealed that Lys33 is the PEGylated position for PEG‐mIL‐11. Bioactivity of PEG‐mIL‐11 assessed by B9‐11 cell proliferation assay was comparable to that of mIL‐11. More than 79‐fold increase in area‐under‐the curve (AUC) and 26‐fold increase in maximum plasma concentration (Cmax) was observed in pharmacokinetic analysis. Single dose administration of the PEG‐mIL‐11 induced blood platelets number increase and the effect duration were comparable to that of 7 to 10 consecutive daily administration of mIL‐11 to the normal and thrombocytopenic monkey models. PEG‐mIL‐11 is a promising therapeutic for thrombocytopenia.