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[125I] -重组人白细胞介素-11的药代动力学:1. 对雄性大鼠皮下给药后的吸收、分布及排泄

Pharmacokinetics of [125I]-recombinant human interleukin-11: 1. Absorption, distribution and excretion after subcutaneous administration to male rats.

作者信息

Uchida T, Aoyama K, Mori K, Usui T, Watanabe T, Takariki Y, Asahara N, Hirose M, Kimura T, Tateishi M, Higuchi S

机构信息

Drug Metabolism Laboratories, Yamanouchi Pharmaceutical Co. Ltd, Tokyo, Japan.

出版信息

Eur J Drug Metab Pharmacokinet. 1998 Jul-Sep;23(3):403-10. doi: 10.1007/BF03192301.

Abstract

Absorption, distribution, metabolism and excretion of [125I]-rhIL-11 (recombinant human interleukin-11) after subcutaneous administration in rats were investigated. After a single administration, the concentration of radioactivity in the tissues was 2-6-fold higher in the liver and kidneys, and slightly higher in the gastrointestinal tract as compared to the plasma concentration. However, since the concentration in the other tissues was lower than the plasma concentration, the transport of rhIL-11 into tissues appeared to be low. Tissue radioactivity rapidly diminished, thus accumulation of rhIL-11 in tissues was thought to be low. Excretion of radioactivity into urine and feces was almost complete 72 h after administration, with 88.5% of the dosed radioactivity being found in urine and 7.9% in feces. When [125I]-rhIL-11 was administered to bile-duct cannulated rats, 44.4% of the dosed radioactivity was excreted into bile up to 48 h after administration. Most radioactivity in bile and urine was found in the TCA supernatant and low molecular weight fraction by HPLC analysis, indicating that rhIL-11 was eliminated from the body by metabolism.

摘要

研究了大鼠皮下注射[125I]-重组人白细胞介素-11(rhIL-11)后的吸收、分布、代谢和排泄情况。单次给药后,肝脏和肾脏组织中的放射性浓度比血浆浓度高2 - 6倍,胃肠道中的放射性浓度略高于血浆浓度。然而,由于其他组织中的浓度低于血浆浓度,rhIL-11向组织中的转运似乎较低。组织放射性迅速降低,因此认为rhIL-11在组织中的蓄积较低。给药后72小时,放射性几乎完全通过尿液和粪便排出,给药剂量的88.5%出现在尿液中,7.9%出现在粪便中。当给胆管插管的大鼠注射[125I]-rhIL-11时,给药后48小时内,给药剂量的44.4%排泄到胆汁中。通过高效液相色谱分析发现,胆汁和尿液中的大部分放射性存在于三氯乙酸上清液和低分子量组分中,表明rhIL-11通过代谢从体内消除。

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