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

Area of Science:

• Pharmacology
• Toxicology
• Medical Devices

Background:

• Anticholinesterase poisoning requires rapid antidote administration.
• Manual intramuscular injection of atropine and pralidoxime chloride can lead to reduced drug absorption rates when co-administered.
• Automatic injectors offer potential for improved drug delivery and absorption.

Purpose of the Study:

• To compare the absorption rates of atropine and pralidoxime chloride when delivered via two different automatic injection devices.
• To evaluate the efficacy of the MARK I autoinjector in enhancing atropine absorption.
• To identify sensitive physiological markers of atropine action.

Main Methods:

• A crossover study involving 20 healthy young males (ages 20-30).
• Sequential intramuscular injection of citrated atropine and pralidoxime chloride (PAMCL) using either a multichambered autoinjector or the MARK I device (delivering drugs to separate sites).
• Assessment of atropine absorption via serum levels and physiological parameters (heart rate, salivary secretion, pupil diameter, near vision accommodation).

Main Results:

• The MARK I device resulted in significantly greater atropine absorption within the first 30 minutes post-injection.
• Salivary secretion changes were identified as a potentially sensitive and convenient marker for atropine's anticholinergic effects.
• The 6.9-mumol dose of atropine demonstrated near-maximal antisialogogue activity in the study population.

Conclusions:

• The MARK I autoinjector enhances atropine absorption, likely due to improved drug dispersal and separation from PAMCL.
• Salivary secretion is a practical and sensitive indicator of atropine's therapeutic effects.
• Automatic injectors represent an advancement in the delivery of antidotes for anticholinesterase poisoning.