{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:52:30Z","timestamp":1791928350541,"version":"4.3.4"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T00:00:00Z","timestamp":1599609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007013","name":"F. Hoffmann-La Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Pharmacologic effects were analysed to determine a dose recommendation for oseltamivir in immunocompromised (IC) adults with influenza.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Quantitative clinical pharmacology methods were applied to data from 160 adult IC patients (aged 18\u201078 years) from two studies (NV20234, 150 patients; NV25118, 10 patients) who received oseltamivir 75\u2010200 mg twice daily for up to 10 days. An established population\u2010pharmacokinetic (PK) model with additional effects on oseltamivir and oseltamivir carboxylate (OC) clearance described the PK characteristics of oseltamivir in IC patients versus otherwise healthy (OwH) patients from previous clinical trials. Estimated PK parameters were used to evaluate exposure\u2010response relationships for virologic endpoints (time to cessation of viral shedding, viral load measures and treatment\u2010emergent resistance). A drug\u2010disease model characterized the viral kinetics of influenza accounting for the effect of OC on viral production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Oseltamivir clearance was 32.5% lower (95% confidence interval [CI], 26.1\u201038.8) and OC clearance was 33.7% lower (95% CI, 23.2\u201044.1) in IC versus OwH patients. No notable exposure\u2010response relationships were identified for exposures higher than those achieved after conventional dose oseltamivir 75 mg, which appeared to be close to the maximum effect of oseltamivir. Simulations of the drug\u2010disease model predicted that initiating treatment within 48 hours of symptom onset had maximum impact, and a treatment duration of 10 days was favourable over 3\u20105 days to limit viral rebound.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings support the use of conventional\u2010dose oseltamivir 75 mg twice daily for 10 days in the treatment of IC adult patients with influenza.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14523","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T12:21:48Z","timestamp":1598617308000},"page":"1359-1368","source":"Crossref","is-referenced-by-count":7,"title":["Pharmacologic effects of oseltamivir in immunocompromised adult patients as assessed by population PK\/PD analysis and drug\u2010disease modelling for dosing regimen optimization"],"prefix":"10.1111","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4866-823X","authenticated-orcid":false,"given":"Stefan","family":"Sturm","sequence":"first","affiliation":[{"name":"Roche Innovation Center Basel, Roche Pharmaceutical Research and Early Development  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabelle","family":"Lemenuel\u2010Diot","sequence":"additional","affiliation":[{"name":"Roche Innovation Center Basel, Roche Pharmaceutical Research and Early Development  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kashyap","family":"Patel","sequence":"additional","affiliation":[{"name":"Certara  Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonid","family":"Gibiansky","sequence":"additional","affiliation":[{"name":"QuantPharm LLC  North Potomac MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajinder","family":"Bhardwaj","sequence":"additional","affiliation":[{"name":"Certara  Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6003-0805","authenticated-orcid":false,"given":"Patrick F.","family":"Smith","sequence":"additional","affiliation":[{"name":"Certara  Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Dang","sequence":"additional","affiliation":[{"name":"Roche Innovation Center New York, Roche Pharmaceutical Research and Early Development  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Zwanziger","sequence":"additional","affiliation":[{"name":"Roche Innovation Center Basel, Roche Pharmaceutical Research and Early Development  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"Nasmyth\u2010Miller","sequence":"additional","affiliation":[{"name":"Roche Products Ltd  Welwyn Garden City Hertfordshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patanjali","family":"Ravva","sequence":"additional","affiliation":[{"name":"Roche Innovation Center New York, Roche Pharmaceutical Research and Early Development  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001432-200208000-00002"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(10)70133-X"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0b013e32833bc1c3"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003343"},{"key":"e_1_2_10_6_1","unstructured":"Tamiflu (oseltamivir) summary of product characteristics.https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/tamiflu-epar-product-information_en.pdf. 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