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使用两种自动注射器装置肌肉注射氯解磷定后阿托品的吸收情况。

Atropine absorption after intramuscular administration with 2-pralidoxime chloride by two automatic injector devices.

作者信息

Friedl K E, Hannan C J, Schadler P W, Jacob W H

机构信息

Department of Clinical Investigation, Madigan Army Medical Center, Tacoma, WA 98431-5454.

出版信息

J Pharm Sci. 1989 Sep;78(9):728-31. doi: 10.1002/jps.2600780905.

Abstract

Compared with manual intramuscular injection, automatic injector delivery substantially enhances drug absorption rate. We examined the effect of two types of automatic injector delivery of two drugs which are components of the standard antidote to anticholinesterase poisoning and which have been previously shown to have a reduced absorption rate when mixed together in a manual injection. In crossover experiments one week apart, 20 nonsmoking healthy young male humans (ages 20-30) were studied after citrated atropine (6.9 mumol/0.7 mL) and pralidoxime chloride (3.5 mmol/2.0 mL; PAMCL) were injected sequentially into a single intramuscular site by either a multichambered autoinjector or a device which delivers the drugs into two separate intramuscular sites (MARK I). Atropine absorption was assessed by the appearance of atropine in the serum and by changes in heart rate, salivary secretion, pupil diameters, and near vision accommodation. Atropine absorption was significantly greater in the first 30 min following injection with the MARK I. The results of this study suggest that: (1) the MARK I device produces a faster absorption of atropine, probably through some combination of its broader dispersal of atropine in the muscle site and its separation of atropine from the PAMCL; (2) salivary secretion may be the most convenient and sensitive marker of atropine action; and (3) the 6.9- mumol (2-mg) dose of atropine delivered by either autoinjector gives near maximal antisialogogue activity in normal male humans.

摘要

与手动肌肉注射相比,自动注射器给药可显著提高药物吸收率。我们研究了两种自动注射器给药方式对两种药物的影响,这两种药物是抗胆碱酯酶中毒标准解毒剂的成分,之前的研究表明,将它们混合进行手动注射时吸收率会降低。在间隔一周的交叉实验中,20名不吸烟的健康年轻男性(年龄20 - 30岁)在枸橼酸阿托品(6.9 μmol/0.7 mL)和氯解磷定(3.5 mmol/2.0 mL;PAMCL)通过多腔自动注射器或一种将药物注射到两个不同肌肉部位的装置(MARK I)依次注射到单个肌肉部位后接受了研究。通过血清中阿托品的出现以及心率、唾液分泌、瞳孔直径和近视力调节的变化来评估阿托品的吸收情况。注射后最初30分钟内,MARK I给药方式下阿托品的吸收明显更高。本研究结果表明:(1)MARK I装置能使阿托品吸收更快,可能是由于其在肌肉部位更广泛地分散阿托品以及将阿托品与PAMCL分离的某种组合;(2)唾液分泌可能是阿托品作用最方便且敏感的指标;(3)两种自动注射器给药的6.9 μmol(2 mg)剂量阿托品在正常男性中产生接近最大的抗唾液分泌活性。

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