摘要
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.
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.
基金
Project (Nos.10802054 and 30700149) supported by the National Natural Science Foundation of China
