Clinical and bioavailability studies of sublingually administered atropine sulfate

Introduction: The increased use of organophosphorus (OP) pesticides and the ever increasing possibility of terror groups using nerve agents underscore a need to develop effective and safe antidotes against OP poisoning. The objectives of the present study were to develop a novel atropine sulfate (AS) sublingual injection formulation, to create its bioavailability data in humans and to evaluate its suitability for field use with a view to obtain early therapeutic drug concentration in comparison to the conventional intramuscular route that provides a therapeutic peak of 6 to 8 ng/mL in blood at 30 minutes. Methods: Two milligrams per 0.1 mL of AS was sublingually injected in 6 volunteers, and bioavailability and atropinization signs (blood pressure, pupil diameter, and heart rate) were noted. Results: Human bioavailability curve was created, which was equivalent to 2 mg IM injection in amplitude within 10 minutes and describing a better curve thereafter. Peak plasma concentration of AS occurred at 15 minutes and was 21 ng/mL. Increase in heart rate became extremely significant at 5 minutes (P<.0001) with maximum increase of 62% +/- 6% at 10 minutes after administration. Pupil diameter showed maximal increase of 58% +/- 21% at 15 minutes (P<.01). Conclusions: Sublingual AS appears to have several advantages over conventional IM route including better bioavailability, rapid onset of action, and early atropinization. It is a safe and efficacious procedure with the potential to become an alternative to conventional IM injection, particularly in case of chemical terrorism scenario where hundreds of victims may require immediate atropinization simultaneously. (C) 2010 Elsevier Inc. All rights reserved.