Radiation therapy has been widely applied in cancer treatment.However,it often causes thrombocytopenia (deficiency of white blood cells) as an adverse effect.Recombinant human interleukin-6 (rhIL-6) has been found to be a very effective way against this thrombocytopenia,but IL-6 has low stability in blood,which reduces its efficacy.To increases the stability and half-life of rhIL-6,it was modified by polyethylene glycol (PEG).The pharmacokinetics and the tissue distribution of PEG-rhIL-6 labeled with 125I were examined after subcutaneous injection in rats.The pharmacokinetic pattern of PEG-rhIL-6 was defined with linear-kinetics,and we fitted a one-compartment model with half-lives of 10.44–11.37 h (absorption,t1/2Ka) and 19.77–21.53 h (elimination,t1/2Ke),and peak concentrations at 20.51–21.96 h (tpeak) in rats.Half-lives and tpeak of PEG-rhIL-6 were longer than those of rhIL-6 previously reported.In the present study,for deposition of PEG-rhIL-6 in rats,the tissue distribution examination showed that blood was the major organ involved,rather than liver.However,as to the elimination of PEG-rhIL-6,the major organ was the kidney.The excretion fraction of the injection dose recovered from urine was 23.32% at 192 h after subcutaneous administration.Less than 6% of PEG-rhIL-6 was eliminated via the feces at 192 h.These results indicate that PEG-rhIL-6 is a good candidate drug formulation for patients with cancer.
