Institute of Nuclear Medicine and Allied Sciences, Defence Research & Development Organization, Brig. SK Mazumdar Marg, Delhi 110 054, India.
Am J Emerg Med. 2010 Feb;28(2):143-50. doi: 10.1016/j.ajem.2008.10.025.
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.
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.
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% + or - 6% at 10 minutes after administration. Pupil diameter showed maximal increase of 58% + or - 21% at 15 minutes (P < .01).
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.
有机磷（OP）农药使用的增加以及恐怖组织使用神经毒剂的可能性不断增加，这突显出有必要开发针对 OP 中毒的有效和安全解毒剂。本研究的目的是开发一种新的硫酸阿托品（AS）舌下注射液制剂，在人体中创建其生物利用度数据，并评估其是否适合现场使用，以期与传统的肌肉内途径相比获得早期治疗药物浓度，因为后者在 30 分钟时在血液中提供 6 至 8ng/mL 的治疗峰值。
将 0.1mL 中的 2 毫克 AS 舌下注射到 6 名志愿者中，并记录生物利用度和阿托品化体征（血压、瞳孔直径和心率）。
创建了人体生物利用度曲线，该曲线在 10 分钟内与 2mgIM 注射等效，此后描述了更好的曲线。AS 的血浆峰浓度出现在 15 分钟，为 21ng/mL。给药后 5 分钟心率增加变得非常显著（P<0.0001），最大增加 62%+或-6%在 10 分钟后。瞳孔直径在 15 分钟时显示最大增加 58%+或-21%（P<0.01）。
与传统的 IM 途径相比，舌下 AS 似乎具有几个优势，包括更好的生物利用度、起效迅速和早期阿托品化。这是一种安全有效的程序，有可能成为传统 IM 注射的替代方法，特别是在发生数百名受害者可能需要同时立即进行阿托品化的化学恐怖袭击情况下。
