{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T23:41:19Z","timestamp":1769816479206,"version":"3.49.0"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T00:00:00Z","timestamp":1592265600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007054","name":"MSD","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Finding a suitable treatment for HCV patients with swallowing disorders is still a major challenge. In practice, direct-acting antivirals are crushed without knowledge of adequate absorption. Crushing can alter drug exposure, possibly leading to treatment failure, development of resistance or toxicity. Currently, there is no information about crushing of the fixed-dose combination tablet of elbasvir\/grazoprevir; therefore, crushing of this tablet is not recommended.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To investigate the influence of crushing on the pharmacokinetics of the elbasvir\/grazoprevir fixed-dose combination tablet.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted an open-label, two-period, randomized, cross-over, Phase I, single-dose trial in 11 healthy adult volunteers. Subjects randomly received whole-tablet elbasvir\/grazoprevir or crushed and suspended elbasvir\/grazoprevir in a fasted state. Pharmacokinetic similarity criteria (90% CIs lie within 70%\u2013143% acceptance range) were used for AUC0\u2013\u221e and AUC0\u201372.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Mean plasma concentration\u2013time curves of elbasvir and grazoprevir showed similar pharmacokinetic profiles. The primary pharmacokinetic parameters AUC0\u2013\u221e and AUC0\u201372 of elbasvir and grazoprevir after intake of a crushed tablet were on average 12%\u201316% higher compared with the whole tablet, but 90% CIs were all within the predefined boundaries of pharmacokinetic similarity. Crushing leads to a higher Cmax of grazoprevir (42%); no significant difference was found between treatments with regard to the Cmax of elbasvir. No serious adverse events were reported during the trial.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Pharmacokinetic similarity could be demonstrated for a crushed and suspended tablet compared with a whole tablet, without impacting drug safety or efficacy. Crushed and suspended administration of elbasvir\/grazoprevir can be used in patients with swallowing disorders.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaa230","type":"journal-article","created":{"date-parts":[[2020,5,15]],"date-time":"2020-05-15T11:49:55Z","timestamp":1589543395000},"page":"2661-2665","source":"Crossref","is-referenced-by-count":5,"title":["Pharmacokinetic similarity demonstrated after crushing of the elbasvir\/grazoprevir fixed-dose combination tablet for HCV infection"],"prefix":"10.1093","volume":"75","author":[{"given":"Dani\u00eblle W M","family":"Pijnenburg","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minou","family":"van Seyen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evertine J","family":"Abbink","sequence":"additional","affiliation":[{"name":"Radboudumc Technology Center Clinical Studies, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Colbers","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joost P H","family":"Drenth","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M","family":"Burger","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,6,16]]},"reference":[{"key":"2020082404584283400_dkaa230-B1","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.jhep.2018.03.026","article-title":"EASL recommendations on treatment of hepatitis C 2018","volume":"69","year":"2018","journal-title":"J Hepatol"},{"key":"2020082404584283400_dkaa230-B2","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1007\/s11096-013-9836-2","article-title":"Swallowing difficulties with oral drugs among polypharmacy patients attending community pharmacies","volume":"35","author":"Marquis","year":"2013","journal-title":"Int J Clin Pharm"},{"key":"2020082404584283400_dkaa230-B3","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1007\/s00228-012-1417-0","article-title":"Difficulties swallowing solid oral dosage forms in a general practice 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drug delivery in older people","volume":"135","author":"Lau","year":"2018","journal-title":"Adv Drug Deliv Rev"},{"key":"2020082404584283400_dkaa230-B7","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1016\/j.xphs.2018.02.015","article-title":"A phase 1 study to evaluate the effect of crushing, cutting into half, or grinding of glecaprevir\/pibrentasvir tablets on exposures in healthy subjects","volume":"107","author":"Oberoi","year":"2018","journal-title":"J Pharm Sci"},{"key":"2020082404584283400_dkaa230-B8","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1097\/QAI.0b013e318232b057","article-title":"Pharmacokinetics of lopinavir\/ritonavir crushed versus whole tablets in children","volume":"58","author":"Best","year":"2011","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2020082404584283400_dkaa230-B9","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1093\/jac\/dky191","article-title":"Crushing of dolutegravir fixed-dose combination tablets 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