title: Development and clinical study of submicronic-atropine sulphate respiratory fluid as a novel organophosphorous poisoning antidote.
abstract: BACKGROUND
  Increased use of organophosphate insecticides (OPI) and possibility of terror groups using stocks of nerve agents underscore the need to develop effective and safe antidotes. While intramuscular administration of antidotes like atropine sulphate (AS) has certain lacunae, intravenous route may not be always feasible in emergency field conditions.
  
  
  OBJECTIVE
  Objective was (a) to develop a novel inhalable submicronic-AS respiratory fluid as potential antidote for OPI poisoning, (b) in-vitro and in-vivo evaluation in terms of respiratory fraction, and (c) clinical study to assess drug bioavailability in blood and atropinization pattern post-inhalation.
  
  
  METHODS
  Formulation was optimized on the basis of particle size of aerosolized droplets and in-vitro nebulization rate. Anderson cascade impaction (ACI) studies were carried out to validate the advantage of test formulation in terms of respirable fraction. Six healthy volunteers were inhaled the test formulation and blood bioavailability and atropinization were noted serially. Gamma scintigraphy was used to quantify total and regional lung deposition of nebulized AS in-vivo.
  
  
  RESULTS
  The formulation was optimized using 30% ethanol-saline with particle size in the range of 350-500 nm. In-vitro ACI data showed high respirable fraction (82.6 ± 3.1%) for the test formulation. In-vivo scintigraphy suggested whole lung deposition of 80.2 ± 6.8% of the total inhaled dose. Early blood bioavailability and atropinization pattern confirmed that therapeutic concentration of the drug in blood was reached within 5 min.
  
  
  CONCLUSIONS
  3% submicronic-AS respiratory fluid might be used as potential prophylactic/therapeutic option against OPI poisoning with several advantages over intramuscular injection, including early blood bioavailability and atropinization.
authors.affiliation: a Division of Nuclear Medicine and.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Mittal
authors.affiliation: a Division of Nuclear Medicine and.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Kumar
authors.affiliation: a Division of Nuclear Medicine and.
authors.forename: Harish
authors.initials: H
authors.lastname: Rawat
authors.affiliation: a Division of Nuclear Medicine and.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Jaimini
authors.affiliation: b Division of Health , Institute of Nuclear Medicine and Allied Sciences, Defence R&D Organisation , New Delhi , India.
authors.forename: Mitrabasu
authors.initials: M
authors.lastname: Chhillar
authors.affiliation: a Division of Nuclear Medicine and.
authors.forename: Aseem
authors.initials: A
authors.lastname: Bhatnagar
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000931:Antidotes / Q000008:administration & dosage* / Q000378:metabolism; D001285:Atropine / Q000008:administration & dosage* / Q000378:metabolism; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D006801:Humans; D008168:Lung / Q000187:drug effects*; D008297:Male; D062025:Organophosphate Poisoning / Q000188:drug therapy*; D010316:Particle Size; D011877:Radionuclide Imaging / Q000379:methods
chemical_list: D000931:Antidotes; D001285:Atropine
keywords: Antidote; gamma scintigraphy; inhalation; organophosphorous poisoning; submicronic-atropine sulphate