[1]杨翠红,刘金剑,褚丽萍,等.125I标记注射用干扰素α2b(假单胞菌)研究雾化吸入与肌肉注射的代谢及组织分布差异[J].国际放射医学核医学杂志,2015,39(3):191-196.[doi:10.3760/cma.j.issn.1673-4114.2015.03.001]
　Yang Cuihong,Liu Jinjian,Chu Liping,et al.Pharmacokinetics and tissue distribution of interferon α2b（Pseudomonas putida）administered via atomization inhalation and intramuscular injection by 125I labeling[J].International Journal of Radiation Medicine and Nuclear Medicine,2015,39(3):191-196.[doi:10.3760/cma.j.issn.1673-4114.2015.03.001]
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125I标记注射用干扰素α2b(假单胞菌)研究雾化吸入与肌肉注射的代谢及组织分布差异(/HTML)
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《国际放射医学核医学杂志》[ISSN:1673-4114/CN:12-1381/R]

卷:
39
期数:
2015年第3期
页码:
191-196
栏目:
出版日期:
2015-05-25

文章信息/Info

Title:
Pharmacokinetics and tissue distribution of interferon α2b（Pseudomonas putida）administered via atomization inhalation and intramuscular injection by 125I labeling
作者:
杨翠红1;  刘金剑1;  褚丽萍1;  高红林1;  郑立运2;  张崇远2;  刘利成2;  张玉民1
1. 中国医学科学院放射医学研究所, 天津市放射医学与分子核医学重点实验室, 天津, 300192;
2. 哈药集团生物工程有限公司, 哈尔滨, 150025
Author(s):
Yang Cuihong1;  Liu Jinjian1;  Chu Liping1;  Gao Honglin1;  Zheng Liyun2;  Zhang Chongyuan2;  Liu Licheng2;  Zhang Yumin1
Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Peking Union Medical College, Tianjin 300192, China
关键词:
干扰素α2b; 放射性核素标记; 碘放射性同位素; 药代动力学; 组织分布
Keywords:
Interferon α2b; Radiolabeling; Iodine radioisotopes; Pharmacokinetics; Tissue distribution
DOI:
10.3760/cma.j.issn.1673-4114.2015.03.001
摘要:
目的 比较采用雾化吸入与肌肉注射两种不同方式给药注射用重组人干扰素α2b(假单胞菌)(IFNα2b),其在兔体内的药代动力学和组织分布差异。方法 采用125I标记法对IFNα2b进行放射性核素标记,按45万IU/kg体质量(参考人推荐用量15万IU/kg体重)的剂量分别进行雾化吸入和肌肉注射给药,利用放射性同位素示踪技术研究IFNα2b在大耳白兔体内的药代动力学;在0.5、2、4、8和12h通过活体成像和γ计数检测不同组织和肺脏不同部位的干扰素分布情况。结果 药代动力学结果表明,肌肉注射组的0~24 h的血药浓度-时间曲线下面积(AUC0-24)为(39.20±1.89)ng·h-1·ml-1,平均驻留时间(MRT)为(6.90±0.21)h,清除速率(CL)为(0.09±0.004)ml·kg-1·h-1,半衰期(T1/2)为(7.30±0.38)h;雾化吸入组的AUC0-24为(45.10±4.65)ng·h-1·ml-1,MRT为(16.10±1.37)h,CL为(0.06±0.010)ml·kg-1·h-1,T1/2为(12.10±1.19)h。体内组织分布结果表明,雾化吸入给药方式IFNα2b主要分布在肺中,12 h仍可观察到肺中有放射性信号,而肌肉注射方式在2 h可观察到肾脏中有较高的放射性信号,之后逐渐减弱。结论 雾化吸入给药较肌肉注射给药能够明显延长IFNα2b在体内的作用时间,且肺部药物浓度更高。与常规肌肉注射相比,雾化吸入IFNα2b的给药方式可能对治疗肺部病毒性感染和呼吸道感染具有更长的药物作用时间和更好的疗效。
Abstract:
Objective To compare the in vivo pharmacokinetics and tissue distribution difference of interferon α2b(IFNα2b,Pseudomonas putida) in rabbits administered via atomization inhalation and intramuscular injection.Methods IFNα2b was radiolabeled with iodine-125 and then administered to rabbits at a dose of 450 000 IU/kg body weight(according to the recommended dosage for humans of 150 000 IU/kg body weight) via atomization inhalation and intramuscular injection.The pharmacokinetics of IFNα2b in rabbits was studied using radioisotope tracer technique.The distribution of IFNα2b in different tissues and the different parts of the lung at 0.5,2,4,8,and 12 h was detected by ex vivo imaging and γ-counting methods.Results The pharmacokinetic results showed that the area under the curve,mean retention time,clearance,and half-life time of intramuscular injection group were(39.20±1.89)ng·h-1·ml-1,(6.90±0.21)h,(0.09±0.004)ml·kg-1·h-1,and(7.30±0.38)h,respectively,and the corresponding data of atomization inhalation group were(45.10±4.65)ng·h-1·ml-1,(16.10±1.37)h, (0.06±0.010)ml·kg-1·h-1,and(12.10±1.19)h,respectively.The tissue distribution results indicated that the IFNα2b administered via atomization inhalation was mainly distributed in the lung,with the detectable radioactive signal as long as 12 h.However,high radioactive signals were observed in the kidney in the intramuscular injection group at 2 h,and then the signals gradually diminished.Conclusions Compared with the conventional intramuscular injection,atomization inhalation could evidently prolong the in vivo residence time of IFNα2b and exhibited higher lung accumulation.Consequently,the atomization inhalation of IFNα2b may have better therapeutic effect and longer duration of drug action for pulmonary viral and respiratory tract infections.

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备注/Memo

备注/Memo:
收稿日期:2015-04-13。
基金项目:国家自然科学基金(51203189);北京协和医学院"青年教师项目"(33320140034);中国医学科学院放射医学研究所基金(项目编号:ST1428,SF1530)
通讯作者:张玉民,Email:zhangyumin21@sina.cn
更新日期/Last Update: 1900-01-01