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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 I-125 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.
- 出版日期2011-1
- 单位四川大学; 中国科学院成都生物研究所
