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

Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2011年第1期12卷 32-39页

作者： Xue-ling HE Hai-lin YIN Jiang WU Ke ZHANG Yan LIU Tao YUAN Hai-lin RAO Liang LI Guang YANG Xue-mei ZHANG Institute of Biomedical Engineering West China Center of Medical Sciences Sichuan University Chengdu 610041 China Laboratory Animal Center of Sichuan University Chengdu 610041 China Chengdu Institute of Biological Products China National Biotic Group (CNBG) Chengdu 610023 China

Radiation therapy has been widely applied in cancer ***,it often causes thrombocytopenia (deficiency of white blood cells) as an adverse *** 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 *** 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 *** 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 ***-lives and tpeak of PEG-rhIL-6 were longer than those of rhIL-6 previously *** 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 ***,as to the elimination of PEG-rhIL-6,the major organ was the *** excretion fraction of the injection dose recovered from urine was 23.32% at 192 h after subcutaneous *** than 6% of PEG-rhIL-6 was eliminated via the feces at 192 *** results indicate that PEG-rhIL-6 is a good candidate drug formulation for patients with cancer.

关键词： Polyethylene glycol recombinant human interleukin-6 Pharmacokinetics Rat

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