{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T08:24:46Z","timestamp":1768897486290,"version":"3.49.0"},"reference-count":15,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,3,8]],"date-time":"2013-03-08T00:00:00Z","timestamp":1362700800000},"content-version":"vor","delay-in-days":4602,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2000,8]]},"abstract":"<jats:p>The tolerability and pharmacokinetics of Ro 64\u20130802, a potent, selective inhibitor of influenza neuraminidase, and its oral prodrug oseltamivir were investigated in three double\u2010blind, placebo\u2010controlled studies. Two studies involved healthy adult volunteers (18\u201355 years) (n = 48) who received single (20\u20131000 mg) or bid doses (50\u2013500 mg) (n = 32) of oseltamivir or placebo for 7 days. Healthy elderly volunteers (\u226565 years) (n = 24) received oseltamivir 100 to 200 mg bid or placebo for 7 days in a third study. Measurable plasma concentrations of the active metabolite appeared rapidly in plasma and were significantly higher and longer lasting than those of oseltamivir. Pharmacokinetics of both compounds were linear. Multiple\u2010dose exposure was predictable from single\u2010dose data, and steady\u2010state plasma concentrations were achieved within 3 days of bid drug administration. Oseltamivir was well tolerated at single doses of up to 1000 mg and twice\u2010daily doses of up to 500 mg. Adverse events were mild in intensity. Exposure to both prodrug and active metabolite was increased in elderly patients by approximately 25%. However, due to the wide safety margin of both compounds, no dose adjustment is necessary for elderly patients.<\/jats:p>","DOI":"10.1177\/00912700022009567","type":"journal-article","created":{"date-parts":[[2003,7,19]],"date-time":"2003-07-19T09:38:13Z","timestamp":1058607493000},"page":"836-843","source":"Crossref","is-referenced-by-count":68,"title":["The Pharmacokinetics and Tolerability of the Oral Neuraminidase Inhibitor Oseltamivir (Ro 64\u20130796\/GS4104) in Healthy Adult and Elderly Volunteers"],"prefix":"10.1002","volume":"40","author":[{"given":"Joseph W.","family":"Massarella","sequence":"first","affiliation":[]},{"given":"George Z.","family":"He","sequence":"additional","affiliation":[]},{"given":"Albert","family":"Dorr","sequence":"additional","affiliation":[]},{"given":"Keith","family":"Nieforth","sequence":"additional","affiliation":[]},{"given":"Penelope","family":"Ward","sequence":"additional","affiliation":[]},{"given":"Andy","family":"Brown","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2013,3,8]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199510053331401"},{"issue":"04","key":"e_1_2_1_3_2","first-page":"1","volume":"48","author":"Centers for Disease Control and Prevention: Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP)","year":"1999","journal-title":"MMWR"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-77011-1_8"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(74)90276-1"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/363418a0"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja963036t"},{"key":"e_1_2_1_8_2","doi-asserted-by":"crossref","first-page":"3234","DOI":"10.1128\/AAC.42.12.3234","article-title":"Characterization of human influenza virus variants selected in vitro in the presence of the neuraminidase inhibitor GS 4071","volume":"42","author":"Tai CY","year":"1998","journal-title":"Antimicrob Agents Chemother"},{"issue":"3","key":"e_1_2_1_9_2","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1128\/AAC.42.3.647","article-title":"Identification of GS 4104 as an orally bioavailable prodrug of the influenza virus neuraminidase inhibitor GS 4071","volume":"42","author":"Li W","year":"1998","journal-title":"Antimicrob Agents Chemother"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.9.1949"},{"key":"e_1_2_1_11_2","unstructured":"WiltshireHR MuirJ LambkinR DaviesS:Distribution of the influenza neuraminidase inhibitor GS4071 following oral administration of its prodrug GS4104 in ferrets (abstract). 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