{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T15:54:06Z","timestamp":1777910046363,"version":"3.51.4"},"reference-count":13,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ocular Pharmacology and Therapeutics"],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>Previous pharmacokinetic studies conducted on atropine sulfate ophthalmical solution have utilized bioanalytical assays that lacked sufficient sensitivity to fully characterize the complete pharmacokinetic profile. To address these limitations, Pharma Medica Research Inc. has developed and validated an ultrasensitive bioanalytical method capable of accurately quantifying the active enantiomer, L-hyoscyamine, with a very low limit of quantitation of 0.500 pg\/mL. The objective of this study was to evaluate the pharmacokinetics of L-hyoscyamine in healthy subjects using a highly sensitive bioanalytical assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Ten subjects were administered 0.3 mg of Isopto Atropine solution into the conjunctival sac of the eye. Blood samples were taken as early as 2 min and up to 24 h following administration. The plasma samples were assayed for L-hyoscyamine using a chiral method with an analytical range of 0.500\u2013500 pg\/mL. The pharmacokinetic parameters were estimated using both a noncompartmental and compartmental approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The pharmacokinetics of L-hyoscyamine were fully characterized as there were no samples that were below the limit of quantitation following dosing. Using noncompartmental analysis, the mean C\n                      <jats:sub>max<\/jats:sub>\n                      was 467.9 \u00b1 159.4 pg\/mL with a median (range) T\n                      <jats:sub>max<\/jats:sub>\n                      of 0.5 (0.08\u20131) h. The mean area under the concentration\u2013time curve was 1668.96 \u00b1 436.02 h\u00b7pg\/mL and the mean half-life was 3.91 \u00b1 1.16 h. Overall, the study drug was well tolerated and no serious adverse events were reported.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Through the utilization of a proprietary ultrasensitive bioanalytical method, a comprehensive investigation into the pharmacokinetics of L-hyoscyamine has been successfully conducted. This advanced method offers significant potential for optimizing study designs and facilitating in-depth examinations of the pharmacokinetics of ocularly administered atropine formulations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/jop.2024.0113","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T14:13:46Z","timestamp":1728051226000},"page":"1-7","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Pharmacokinetics of Atropine Administered Ocularly Using an Ultrasensitive Bioanalytical Assay"],"prefix":"10.1177","volume":"41","author":[{"given":"Mohammed","family":"Bouhajib","sequence":"first","affiliation":[{"name":"Pharma Medica Research Inc., Mississauga, Ontario, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zia","family":"Tayab","sequence":"additional","affiliation":[{"name":"Pharma Medica Research Inc., Mississauga, Ontario, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chantal","family":"Di Marco","sequence":"additional","affiliation":[{"name":"Pharma Medica Research Inc., Mississauga, Ontario, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis (Dong-Kyun)","family":"Suh","sequence":"additional","affiliation":[{"name":"Pharma Medica Research Inc., Mississauga, Ontario, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"key":"e_1_3_4_2_2","first-page":"139","article-title":"On the atropine treatment of acquired and progressive myopia","volume":"2","author":"Derby H","year":"1874","unstructured":"Derby H. On the atropine treatment of acquired and progressive myopia. Trans Am Ophthalmol Soc, 1874; 2:139\u2013154.","journal-title":"Trans Am Ophthalmol Soc"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.8b00615"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/aos.13889"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0420.1999.770215.x"},{"key":"e_1_3_4_6_2","first-page":"150","volume-title":"The Pharmacological Basis of Therapeutics","author":"Brown JH","year":"1990","unstructured":"Brown JH. Atropine, scopolamine, and related antimuscarinic drugs. In: Goodman Gliman A, , Rall TW, , Nies AS, , Taylor P. (eds). The Pharmacological Basis of Therapeutics, 8th ed, Macmillan Publishing Company, New York. 1990, pp.150\u2013165.","edition":"8"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-5155(00)00305-1"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.86.11.1306"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-0565"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1988.155"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00543495"},{"key":"e_1_3_4_12_2","unstructured":"OECD Principles of Good Laboratory Practice (as revised in 1997) Guidance for Industry Bioanalytical Method Validation - US Department of Health and Human Services Food and Drug Administration May 2018 and Guideline on Bioanalytical Method Validation - European Medicines Agency EMEA\/CHMP\/EWP\/192217\/2009 Rev. 1 Corr. 2 1 February 2012."},{"key":"e_1_3_4_13_2","unstructured":"FDA Product-Specific Guidance for Generic Drug Development for Atropine Opthalmic Solution. Available from: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/psg\/PSG_206289.pdf [Last Accessed February 2024]."},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10040588"}],"container-title":["Journal of Ocular Pharmacology and Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/jop.2024.0113","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/jop.2024.0113","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/jop.2024.0113","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T14:46:40Z","timestamp":1777646800000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/jop.2024.0113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,1]]},"references-count":13,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1,1]]}},"alternative-id":["10.1089\/jop.2024.0113"],"URL":"https:\/\/doi.org\/10.1089\/jop.2024.0113","relation":{},"ISSN":["1080-7683","1557-7732"],"issn-type":[{"value":"1080-7683","type":"print"},{"value":"1557-7732","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,1]]}}}