TRANSDERMAL PENETRATION OF THE ACETYLCHOLINESTERASE REACTIVATOR HI-6 IN A RAT MODEL
Military Medical Science Letters(2013)
摘要
The objective of the experiment was to verify that HI-6 dimethanesulphonate (HI-6 DMS) is able to penetrate the skin in amounts sufficient to protect against organophosphate poisoning using a rat model.HI-6 2Cl is a major component of Transant, a transdermal patch, used as a protective agent against organophosphate intoxication in the Czech and Slovak armies, although there is little evidence that HI-6 would penetrate the skin in sufficient amounts.HI-6 DMS at a total amount of 127 mg or 635 mg was applied as a buffer solution on the Transant patch which was fixed on the back of the rat.Two, seven or twenty-four hours later, rats were sacrificed and blood samples were collected to determine the levels of HI-6 in plasma by HPLC on reversed phase with isocratic elution and UV/VIS detection.HI-6 was not detectable in plasma samples of animals exposed to 127 mg of HI-6 DMS.The highest levels of HI-6 (20.6 ± 18.8 ng/ml) were found in plasma of animals exposed to 635 mg of HI-6 DMS 2 hours after patch application, whereas after 7 or 24 hours the levels were very low.Based on these results, the ability of HI-6 DMS to penetrate the skin is discussed and some possibilities of improving the transdermal penetration are suggested.
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Chemical Warfare Agents
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