A multiple-dose pharmacokinetics of polyethylene glycol recombinant human interleukin-6 (PEG-rhIL-6) in rats |
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Authors: | He Xue-ling Yin Hai-lin Wu Jiang Zhang Ke Liu Yan Yuan Tao Rao Hai-lin Li Liang Yang Guang Zhang Xue-mei |
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Affiliation: | Institute of Biomedical Engineering, West China Center of Medical Sciences, Sichuan University, Chengdu 610041, China. hxlscu@163.com |
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Abstract: | 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, t 1/2K a) and 19.77–21.53 h (elimination, t 1/2Ke), and peak concentrations at 20.51–21.96 h (t peak) in rats. Half-lives and t peak 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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Keywords: | Polyethylene glycol Recombinant human interleukin-6 Pharmacokinetics Rat |
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