Systemic Bioavailability of Sublingual Atropine Ophthalmic Solution: a Phase I Study in Healthy Volunteers with Implications for Use as a Contingency Medical Countermeasure.
| Autor: | Schwartz MD; Biomedical Advanced Research and Development Authority (BARDA), Office of the Assistant Secretary for Preparedness and Response (ASPR), Department of Health and Human Services (HHS), 200 C St., SW, Washington, DC, 20024, USA. Michael.schwartz@hhs.gov., Raulli R; Biomedical Advanced Research and Development Authority (BARDA), Office of the Assistant Secretary for Preparedness and Response (ASPR), Department of Health and Human Services (HHS), 200 C St., SW, Washington, DC, 20024, USA., Laney JW; Biomedical Advanced Research and Development Authority (BARDA), Office of the Assistant Secretary for Preparedness and Response (ASPR), Department of Health and Human Services (HHS), 200 C St., SW, Washington, DC, 20024, USA., Coley W; Biomedical Advanced Research and Development Authority (BARDA), Office of the Assistant Secretary for Preparedness and Response (ASPR), Department of Health and Human Services (HHS), 200 C St., SW, Washington, DC, 20024, USA., Walker R; Biomedical Advanced Research and Development Authority (BARDA), Office of the Assistant Secretary for Preparedness and Response (ASPR), Department of Health and Human Services (HHS), 200 C St., SW, Washington, DC, 20024, USA., O'Rourke AW; Biomedical Advanced Research and Development Authority (BARDA), Office of the Assistant Secretary for Preparedness and Response (ASPR), Department of Health and Human Services (HHS), 200 C St., SW, Washington, DC, 20024, USA., Raine K; Biomedical Advanced Research and Development Authority (BARDA), Office of the Assistant Secretary for Preparedness and Response (ASPR), Department of Health and Human Services (HHS), 200 C St., SW, Washington, DC, 20024, USA., Horwith G; Biomedical Advanced Research and Development Authority (BARDA), Office of the Assistant Secretary for Preparedness and Response (ASPR), Department of Health and Human Services (HHS), 200 C St., SW, Washington, DC, 20024, USA., Gao Y; Biomedical Advanced Research and Development Authority (BARDA), Office of the Assistant Secretary for Preparedness and Response (ASPR), Department of Health and Human Services (HHS), 200 C St., SW, Washington, DC, 20024, USA., Eisnor DL; Biomedical Advanced Research and Development Authority (BARDA), Office of the Assistant Secretary for Preparedness and Response (ASPR), Department of Health and Human Services (HHS), 200 C St., SW, Washington, DC, 20024, USA., Lu D; Biomedical Advanced Research and Development Authority (BARDA), Office of the Assistant Secretary for Preparedness and Response (ASPR), Department of Health and Human Services (HHS), 200 C St., SW, Washington, DC, 20024, USA., Wolling B; Biomedical Advanced Research and Development Authority (BARDA), Office of the Assistant Secretary for Preparedness and Response (ASPR), Department of Health and Human Services (HHS), 200 C St., SW, Washington, DC, 20024, USA., David G; Rho Federal Systems Division, Inc., 2635 E NC Highway 54, Durham, NC, 27713-2230, USA., Johnson K; Rho Federal Systems Division, Inc., 2635 E NC Highway 54, Durham, NC, 27713-2230, USA., Barry WT; Rho Federal Systems Division, Inc., 2635 E NC Highway 54, Durham, NC, 27713-2230, USA., Chang J; Rho Federal Systems Division, Inc., 2635 E NC Highway 54, Durham, NC, 27713-2230, USA., Jepson B; Rho Federal Systems Division, Inc., 2635 E NC Highway 54, Durham, NC, 27713-2230, USA., Fein M; High Point Clinical Trials Center, 4160 Mendenhall Oaks Pkwy #105, High Point, NC, 27265, USA. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of medical toxicology : official journal of the American College of Medical Toxicology [J Med Toxicol] 2022 Jul; Vol. 18 (3), pp. 187-197. Date of Electronic Publication: 2022 Mar 21. |
| DOI: | 10.1007/s13181-021-00873-0 |
| Abstrakt: | Introduction: Atropine sulfate is an FDA-approved medical countermeasure (MCM) for the treatment of organophosphorus nerve agent and organophosphate pesticide toxicity. Sufficient MCM supplies must be available in an incident involving a mass human exposure either from an accidental chemical release or a terrorist attack. Methods: We performed a randomized, 3-sequence, 3-period phase I crossover study to assess the bioavailability and pharmacokinetics (PK) of a single dose (0.5 mg and 1.0 mg) of 1% ophthalmic atropine sulfate solution administered sublingually to 15 healthy adult volunteers. The primary endpoint was evaluation of the bioavailability of each of the two sublingual doses against a 1.0 mg reference intravenous (IV) atropine dose. Secondary endpoints included the safety and tolerability (xerostomia scale) of atropine sulfate administered sublingually. Results: Sublingual atropine was safe (no severe AEs or SAEs were reported with either dose) and well tolerated, with a single subject reaching maximum xerostomia on a single dosing day. The geometric mean AUC Conclusion: Sublingual atropine sulfate 1% ophthalmic solution may be an alternative formulation and route of administration combination which expands the capacity and dosing options of atropine as a nerve agent MCM. (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.) |
| Databáze: | MEDLINE |
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