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干扰素:药代动力学与毒性

Interferon: pharmacokinetics and toxicity.

作者信息

Scott G M

出版信息

Philos Trans R Soc Lond B Biol Sci. 1982 Sep 24;299(1094):91-107. doi: 10.1098/rstb.1982.0109.

Abstract

Interferons disappear rapidly from the serum of animals and man, and the kidney may be the major site of interferon destruction. The relevance of serum levels of interferons to their therapeutic activity has not been clearly established, particularly as the stimulation of host defence mechanisms by interferons may be important. Relatively low serum levels of antiviral activity are seen after intramuscular injections of fibroblast interferon compared with those after the same dose of leucocyte interferon. Injections of very pure leucocyte and lymphoblastoid interferons from several sources cause fever, headaches, malaise and myalgia associated with a corticosteroid response and probably with inflammatory prostaglandin synthesis. These reactions become less with repeated dosing but very large doses of lymphoblastoid interferon have been shown to cause liver damage and serious metabolic disturbances. Treatment with moderate doses of exogenous interferons may occasionally be associated with the development of neutralizing antibodies.

摘要

干扰素在动物和人类血清中迅速消失,肾脏可能是干扰素破坏的主要部位。血清中干扰素水平与其治疗活性之间的相关性尚未明确确立,特别是因为干扰素对宿主防御机制的刺激可能很重要。与相同剂量的白细胞干扰素相比,肌肉注射成纤维细胞干扰素后血清中抗病毒活性水平相对较低。注射来自多个来源的非常纯的白细胞和淋巴母细胞样干扰素会引起发热、头痛、不适和肌痛,这些症状与皮质类固醇反应有关,可能还与炎症性前列腺素合成有关。随着重复给药,这些反应会减轻,但已表明非常大剂量的淋巴母细胞样干扰素会导致肝损伤和严重的代谢紊乱。用中等剂量的外源性干扰素治疗偶尔可能会出现中和抗体。

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