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[干扰素——其给药方法及与药代动力学相关的不良反应]

[Interferons--its method of administration and adverse effect related to pharmacokinetics ].

作者信息

Furue H

出版信息

Gan To Kagaku Ryoho. 1984 Feb;11(2):186-93.

PMID:6582804
Abstract

The potential role of interferons in the treatment of malignant diseases is currently being evaluated. This paper reviews experimental and clinical findings regarding pharmacokinetics, method of administration, and side reactions of interferons. Interferon in the blood is rapidly cleared from the circulation. Intramuscular injection of alpha-interferon causes low but stable interferon levels in the blood. However, in the case of beta-interferon, interferon is never detected consistently in the blood after intramuscular or subcutaneous administration. The studies with animal models suggest that doses higher than those given in current clinical trials will be necessary to obtain clearly beneficial effects in human. The maximum safely tolerated daily dose is appreciably higher than that used in most previous studies, although even at this level, considerable toxicity may be encountered. Adequate method of administration, route, dose and interval are not yet established at all. Exact mechanism of anticancer activity is not yet well defined. The most frequent side reaction is fever. However, the exact mechanism to cause these side reactions is also not yet clarified. Dose limiting central nervous system toxicities, hypotension, hypocalcaemia etc. are occasionally encountered in some instances. Antibody to interferon is demonstrated in some cases. Purification of interferon does not always causes reduction of side reactions. The treatment of cancer cases with interferon has just started and there are many problems to be solved. However, therapeutic beneficial may be achieved in the treatment of malignant tumors by appropriate combinations of interferon with conventional treatment. More laboratory studies as well as carefully controlled clinical observations are warranted.

摘要

目前正在评估干扰素在恶性疾病治疗中的潜在作用。本文综述了关于干扰素的药代动力学、给药方法及副作用的实验和临床研究结果。血液中的干扰素会迅速从循环中清除。肌肉注射α-干扰素可使血液中的干扰素水平较低但保持稳定。然而,对于β-干扰素,肌肉注射或皮下注射后在血液中从未持续检测到干扰素。动物模型研究表明,要在人体中获得明显有益效果,需要高于当前临床试验所用的剂量。最大安全耐受日剂量明显高于大多数先前研究中使用的剂量,尽管即便在此剂量水平,仍可能会出现相当大的毒性。给药的适当方法、途径、剂量和间隔根本尚未确定。抗癌活性的确切机制也尚未明确界定。最常见的副作用是发热。然而,导致这些副作用的确切机制也尚未阐明。在某些情况下偶尔会出现剂量限制性中枢神经系统毒性、低血压、低钙血症等。在一些病例中检测到了针对干扰素的抗体。干扰素的纯化并不总能减少副作用。用干扰素治疗癌症病例才刚刚开始,还有许多问题有待解决。然而,通过将干扰素与传统治疗适当联合,在恶性肿瘤治疗中可能会取得治疗益处。需要进行更多的实验室研究以及精心控制的临床观察。

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