{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:36:16Z","timestamp":1787567776345,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    To compare the pharmacokinetics, bioavailability, tolerability, and safety of a novel 4 mg rivastigmine nasal spray to 3 mg rivastigmine oral capsule, a single\u2010dose, open\u2010label, randomized, crossover study was conducted in 16 fasted healthy young men (18 to 55 years). Mean (SD) rivastigmine C\n                    <jats:sub>max<\/jats:sub>\n                    was 8.39 (6.8) and 13.77 (10.7) ng\/mL for oral and nasal, respectively. Rivastigmine AUC\n                    <jats:sub>0\u2010inf<\/jats:sub>\n                    was 19.6 (14.9) and 40.6 (24.4) ng h\/mL for oral and nasal, respectively. The ratio of LS means (nasal test \/ oral reference; 90% C.I.) for rivastigmine C\n                    <jats:sub>max<\/jats:sub>\n                    was 185.83% (134.22, 257.28) and for rivastigmine AUC\n                    <jats:sub>0\u2010inf<\/jats:sub>\n                    was 257.35% (197.26, 335.73). Rivastigmine t\n                    <jats:sub>max<\/jats:sub>\n                    for nasal (0.7 h) was significantly lower than oral (1.2 h,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a0.05), however, NAP226\u201090 t\n                    <jats:sub>max<\/jats:sub>\n                    for nasal (1.9 h) and oral (1.8 h) were similar. NAP226\u201090 C\n                    <jats:sub>max<\/jats:sub>\n                    was 3.93 (1.1) and 3.01 (0.8) ng\/mL for oral and nasal, respectively. NAP226\u201090 AUC\n                    <jats:sub>0\u2010inf<\/jats:sub>\n                    was 22.9 (5.3) and 23.2 (5.1) ng h\/mL for oral and nasal, respectively. Median NAP226\u201090 to rivastigmine AUC\n                    <jats:sub>0\u2010inf<\/jats:sub>\n                    ratio for nasal (0.55) was significantly lower than oral (1.38,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a0.05) because nasal bypassed first\u2010pass metabolism. Both single\u2010dose treatments were safe and well tolerated. Nasal and throat irritation were mostly perceived as mild and transient following nasal administration. The 4 mg rivastigmine nasal spray had 1.5\u2010 and 2.0\u2010fold higher dose normalized rivastigmine C\n                    <jats:sub>max<\/jats:sub>\n                    and AUC\n                    <jats:sub>0\u2010inf<\/jats:sub>\n                    , respectively, and 2.5\u2010fold lower NAP226\u201090 to rivastigmine AUC\n                    <jats:sub>0\u2010inf<\/jats:sub>\n                    ratio compared to 3 mg oral capsule. This nasal spray has good potential to improve the local and gastrointestinal tolerability of rivastigmine treatment in Alzheimer's and Parkinson's disease dementia patients.\n                  <\/jats:p>","DOI":"10.1002\/jcph.70086","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T13:38:39Z","timestamp":1753969119000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacokinetics and Bioavailability of a Novel Rivastigmine Nasal Spray Compared to Rivastigmine Oral Capsule in Healthy Men"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1616-6238","authenticated-orcid":false,"given":"Timothy M.","family":"Morgan","sequence":"first","affiliation":[{"name":"Lachesis Biosciences Ltd.  Breakwater Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Snyder","sequence":"additional","affiliation":[{"name":"Nucleus Network, Department of General Medicine Alfred Health  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32205-4"},{"issue":"4","key":"e_1_2_9_3_1","article-title":"Rivastigmine for Alzheimer's disease","author":"Birks JS","year":"2015","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa041470"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.1998.tb00645.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/gps.1788"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-2918(98)80127-6"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200241030-00006"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2008.09.001"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00221-014-3985-y"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002512-200118110-00006"},{"key":"e_1_2_9_12_1","unstructured":"US FDA.NDA 20\u2013823. 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