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A multiple-dose pharmacokinetics of polyethylene glycol recombinant human interleukin-6 (PEG-rhIL-6) in rats

Xue-ling HE1,2,Hai-lin YIN2,Jiang WU1,Ke ZHANG3,Yan LIU2,Tao YUAN3,Hai-lin RAO3,Liang LI1,Guang YANG2,Xue-mei ZHANG3 (1Institute of Biomedical Engineering,West China Center of Medical Sciences,Sichuan University,Chengdu 610041,China) (2Laboratory Animal Center of Sichuan University,Chengdu 610041,China) (3Chengdu Institute of Biological Products,China National Biotic Group (CNBG),Chengdu 610023,China)  
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.
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