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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Rajpal, Sheetal Mittal, Gaurav Sachdeva, Ruchi Chhillar, Mitrabasu Ali, Rashid Agrawal, Shyam Sunder Kashyap, Ravi Bhatnagar, Aseem |
| Description | Country affiliation: India Author Affiliation: Rajpal S ( Delhi Institute of Pharmaceutical Sciences and Research, Pushp Vihar, Delhi 110 017, India.) |
| Abstract | INTRODUCTION: The increased use of organophosphate (OP) insecticides and the ever increasing possibility of terror groups using nerve agents underscore the need to develop effective and safe antidotes against OP poisoning. While intramuscular administration of nerve gas antidotes like atropine sulphate has certain lacunae, intravenous route is neither practical nor feasible in the field conditions for mass casualties. The objective was to develop a novel atropine sulphate nasal drop formulation, evaluate and characterize it using scintigraphy and to carry out safety-efficacy study in human volunteers with a view to obtain early pharmacological effects in comparison to the existing options, particularly the conventional intramuscular route. METHODS: Permeability studies were done using atropine sulphate solution containing variable amount of chitosan. Radiometric method was developed for scintigraphy studies while standard spectroscopy was used for the quantification of atropine sulphate in fluids. Concentration of atropine sulphate in nasal drops to produce therapeutic concentration in blood was calculated. Six volunteers (age range 18-53 years) were administered the formulation delivering 6mg of atropine sulphate each. Bioavailability and atropinization were noted serially. RESULTS: Based on the results of in vitro, human scintigraphy and analytical data, 1% atropine sulphate-0.5% chitosan was chosen as the final nasal formulation. Human bioavailability curve was created which showed that the therapeutic concentration of the drug in blood was reached within 5min with nasal drops suggesting that drug delivery through the nasal route is significantly better than the intramuscular route. Unpaired t-test between the means of baseline value of heart rate and that of each time interval showed that increase in heart rate of all the volunteers became significant at 15min (P<0.01) and extremely significant at 30min (P<0.001). Correlation was evident from 5min (c>0.7). Pupil diameter showed maximal increase at 30min (P<0.01). CONCLUSIONS: This novel product, 1% atropine sulphate-0.5% chitosan nasal drops might be a safe and efficacious emergency treatment of organophosphorous poisoning with several advantages over the present management, including early atropinization and capability of mass treatment in least amount of time. |
| File Format | HTM / HTML |
| ISSN | 13826689 |
| Issue Number | 2 |
| Journal | Environmental Toxicology and Pharmacology |
| Volume Number | 27 |
| e-ISSN | 18727077 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2009-03-01 |
| Publisher Place | Netherlands |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Environmental Health Discipline Pharmacology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Health, Toxicology and Mutagenesis Medicine Toxicology Pharmacology |
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