title: A multiple-dose pharmacokinetics of polyethylene glycol recombinant human interleukin-6 (PEG-rhIL-6) in rats.
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 (125)I 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(1/2Ka)) 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.
authors.affiliation: Institute of Biomedical Engineering, West China Center of Medical Sciences, Sichuan University, Chengdu 610041, China. hxlscu@163.com
authors.forename: Xue-ling
authors.initials: XL
authors.lastname: He
authors.forename: Hai-lin
authors.initials: HL
authors.lastname: Yin
authors.forename: Jiang
authors.initials: J
authors.lastname: Wu
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Yuan
authors.forename: Hai-lin
authors.initials: HL
authors.lastname: Rao
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Xue-mei
authors.initials: XM
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004337:Drug Carriers; D005260:Female; D006207:Half-Life; D006801:Humans; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes; D008297:Male; D011092:Polyethylene Glycols; D055550:Protein Stability; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D013921:Thrombocytopenia / Q000517:prevention & control; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; C508600:IL6 protein, human; D015850:Interleukin-6; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D011092:Polyethylene Glycols