rG·CSF is a recombinant human granulo cyte colony-stimulating factor (rhG-CSF) produced in CHO cells. rG·CSF is a glycoprotein which has one O-linked sugar chain. We have studied the role of this sugar chain on the disposition of rG·CSF using enzymatically deglycosylated rG·CSF (degly-rG·CSF) and rhG-CSF produced in E. coli (Eco-rG-CSF).
1. rG·CSF or degly-rG·CSF was administered to rats at the dose of 10μg/kg intravenously and subcutaneously. After intravenous administration, the pharmacokinetic parameters (T1/2 (α), T1/2 (β), MRT, Vc and Vss) of two G-CSFs were not significantly different between each other except that the AUC in rG·CSF was greater and the CLtotal in rG·CSF was smaller than those in degly-rG·CSF. After subcutaneous administration, T1/2 and MRT in degly-rG·CSF were significantly smaller than those parameters in rG·CSF. Mean absorption time (MAT) and absolute bioavailability (F) in degly-rG·CSF were smaller than those in rG·CSF.
2. rG·CSF or Eco-rG-CSF was administered to rats at the dose of 10μg/kg intravenously and subcutaneously. After intravenous administration, the pharmacokinetic parameters of two G-CSFs were not significantly different between each other except that the AUC in rG·CSF was greater and the CLtotal in rG·CSF was smaller than those in Eco-rG-CSF. After subcutaneous administration, T1/2, MRT and AUC in Eco-rG-CSF were significantly smaller than those parameters in rG·CSF, respectively. MAT and F in Eco-rG-CSF were smaller than those in rG·CSF.
3. These results showed that after intravenous administration, there were little changes related to sugar chain. These results also suggested that sugar chain contributed to stabilization of rG·CSF at the administration site and delayed absorption of rG·CSF from the administration site after subcutaneous administration. Thus, the sugar chain of rG·CSF seemed to play a role in the elongation of plasma concentration after subcutaneous administration.
