Transdermal Penetration of the Acetylcholinesterase Reactivator Hi-6 in a Rat Model

Abstract

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.

Cholinesterase reactivators and bioscavengers for pre‐ and post‐exposure treatments of organophosphorus poisoning

“…However, its efficacy has not been completely established, and more works are needed to optimize transdermal delivery of positively charged reactivators (Kracmarova et al . ). Further animal and pharmacokinetics‐pharmacodynamics studies are needed to determine whether anti‐Alzheimer disease drugs and oximes alone or in association are better than carbamates as protectants against NAs.…”

Cholinesterase reactivators and bioscavengers for pre‐ and post‐exposure treatments of organophosphorus poisoning

“…However, its efficacy has not been completely established, and more works are needed to optimize transdermal delivery of positively charged reactivators (Kracmarova et al . ). Further animal and pharmacokinetics‐pharmacodynamics studies are needed to determine whether anti‐Alzheimer disease drugs and oximes alone or in association are better than carbamates as protectants against NAs.…”

Cholinesterase reactivators and bioscavengers for pre‐ and post‐exposure treatments of organophosphorus poisoning

“…However, its efficacy has not been completely established, and more works are needed to optimize transdermal delivery of positively charged reactivators (Kracmarova et al . ). Further animal and pharmacokinetics‐pharmacodynamics studies are needed to determine whether anti‐Alzheimer disease drugs and oximes alone or in association are better than carbamates as protectants against NAs.…”

Cholinesterase reactivators and bioscavengers for pre‐ and post‐exposure treatments of organophosphorus poisoning

“…However, its efficacy has not been completely established, and more works are needed to optimize transdermal delivery of positively charged reactivators (Kracmarova et al . ). Further animal and pharmacokinetics‐pharmacodynamics studies are needed to determine whether anti‐Alzheimer disease drugs and oximes alone or in association are better than carbamates as protectants against NAs.…”