{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T03:41:47Z","timestamp":1779334907156,"version":"3.51.4"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"8","funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Kidney Diseases at the National Institutes of Health","award":["R03 DK 096121"],"award-info":[{"award-number":["R03 DK 096121"]}]},{"DOI":"10.13039\/100000060http:\/\/dx.doi.org\/10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060http:\/\/dx.doi.org\/10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Ribavirin concentrations may impact hepatitis C virus (HCV) treatment outcome. We modelled ribavirin serum and intracellular ribavirin monophosphate (RBV-MP) and ribavirin triphosphate (RBV-TP) pharmacokinetics in red blood cells (RBC) using samples collected during the NIAID SPARE trial to explore associations with treatment outcome and the development of anaemia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients and methods<\/jats:title>\n                  <jats:p>Individuals infected with HCV genotype 1 (GT1) received 400 mg of sofosbuvir and either low-dose or weight-based ribavirin as part of the NIAID SPARE trial. Concentrations were modelled using NONMEM and associated with treatment outcomes using unpaired t-tests or Pearson's rho correlations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Average day 14 RBV-MP concentrations were higher in subjects with haemoglobin nadir &amp;lt;10 g\/dL relative to patients with haemoglobin nadir \u226510 g\/dL (6.54 versus 4.48 pmol\/106 cells; P\u200a=\u200a0.02). Additionally, day 14 RBV-MP average concentrations trended towards being higher in subjects that achieved sustained virological response (SVR) as compared with patients who relapsed (4.97 versus 4.09 pmol\/106 cells; P\u200a=\u200a0.07). Receiver operating characteristic curves suggested day 14 RBV-MP concentration thresholds of 4.4 pmol\/106 cells for SVR (P\u200a=\u200a0.06) and 6.1 pmol\/106 cells for haemoglobin nadir &amp;lt;10 versus \u226510 g\/dL (P\u200a=\u200a0.02), with sensitivity and specificity \u226560%. Dosing simulations showed that 800 mg of ribavirin once daily produced day 14 RBV-MP concentrations within the 4.4\u20136.1 pmol\/106 cells range.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>RBV-MP concentrations in RBC at day 14 were related to anaemia and SVR. A therapeutic range was identified for RBV-MP in persons with HCV GT1 disease receiving 24 weeks of sofosbuvir plus ribavirin, suggesting a potential pharmacological basis for individualized ribavirin dosing in IFN-free regimens.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkv122","type":"journal-article","created":{"date-parts":[[2015,5,14]],"date-time":"2015-05-14T00:50:39Z","timestamp":1431564639000},"page":"2322-2329","source":"Crossref","is-referenced-by-count":23,"title":["Serum and cellular ribavirin pharmacokinetic and concentration\u2013effect analysis in HCV patients receiving sofosbuvir plus ribavirin"],"prefix":"10.1093","volume":"70","author":[{"given":"Joseph E.","family":"Rower","sequence":"first","affiliation":[{"name":"1 \u00a0Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric G.","family":"Meissner","sequence":"additional","affiliation":[{"name":"2 \u00a0Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, NIAID, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leah C.","family":"Jimmerson","sequence":"additional","affiliation":[{"name":"1 \u00a0Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anu","family":"Osinusi","sequence":"additional","affiliation":[{"name":"2 \u00a0Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, NIAID, Bethesda, MD, USA"},{"name":"3 \u00a0Gilead Sciences Inc., Foster City, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zayani","family":"Sims","sequence":"additional","affiliation":[{"name":"2 \u00a0Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, NIAID, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tess","family":"Petersen","sequence":"additional","affiliation":[{"name":"2 \u00a0Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, NIAID, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lane R.","family":"Bushman","sequence":"additional","affiliation":[{"name":"1 \u00a0Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela","family":"Wolfe","sequence":"additional","affiliation":[{"name":"4 \u00a0School of Public Health, University of Colorado, Aurora, CO, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John G.","family":"McHutchison","sequence":"additional","affiliation":[{"name":"3 \u00a0Gilead Sciences Inc., Foster City, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shyamasundaran","family":"Kottilil","sequence":"additional","affiliation":[{"name":"2 \u00a0Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, NIAID, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer J.","family":"Kiser","sequence":"additional","affiliation":[{"name":"1 \u00a0Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,5,13]]},"reference":[{"key":"2022020121043764200_DKV122C1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.dld.2010.10.007","article-title":"Ribavirin for chronic hepatitis C: and the mystery goes 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