Administration route dependency of distribution of PEGylated recombinant human tumor necrosis factor binding protein (rhTNFbp-PEG20K dimer) following i.v. and s.c. injection in rats

Abstract

Administration route dependency on the distribution of PEGylated recombinant human tumor necrosis factor binding protein (rhTNFbp-PEG20K dimer) was observed following a subcutaneous (sc) and an intravenous (iv) administrationin rats. rhTNFbp-PEG20K dimer is composed of two rhTNFbp molecules (molecular weight 18,278 daltons each) joined by polyethylene glycol 2000 (PEG20K). The steady state distribution volume of rhTNFbp-PEG20K was 55 ml/kg and 359 ml/kg following the i.v. and s.c. administrations, respectively. These results suggest that the distribution of rhTNFbp-PEG20K is limited within the capillary space after i.v. administration, while rhTNFbp-PEG20K can distribute into a space (35.9% of body weight) which is between extracellular space and total body water. A lymphatic absorption may play a role in the distribution of rhTNFbp-PEG20K dimer following the sc administration. The present study suggests that the administration route of large protein molecule should be determined depending upon target sites.