{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T10:33:31Z","timestamp":1761561211987,"version":"build-2065373602"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T00:00:00Z","timestamp":1325808000000},"content-version":"vor","delay-in-days":1466,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2008,1]]},"abstract":"<jats:p><jats:bold>Study Objectives.<\/jats:bold> To assess the effect of omeprazole on the multiple\u2010dose (steady\u2010state) pharmacokinetics and safety of nelfinavir, and to evaluate the safety and tolerability of nelfinavir when administered alone and with omeprazole.<\/jats:p><jats:p><jats:bold>Design.<\/jats:bold> Open\u2010label, two\u2010period, single\u2010fixed\u2010sequence study.<\/jats:p><jats:p><jats:bold>Setting.<\/jats:bold> Clinical research unit of a large, teaching hospital.<\/jats:p><jats:p><jats:bold>Participants.<\/jats:bold> Twenty healthy volunteers (mean age 26 \u00b1 9 yrs, range 18\u201348 yrs).<\/jats:p><jats:p><jats:bold>Intervention.<\/jats:bold> Subjects received nelfinavir 1250 mg every 12 hours for 4 days (period 1). After a 7\u2010day washout period, subjects were coadministered nelfinavir 1250 mg every 12 hours and omeprazole 40 mg every 24 hours for 4 days (period 2).<\/jats:p><jats:p><jats:bold>Measurements and Main Results.<\/jats:bold> The pharmacokinetics of nelfinavir and its active metabolite M8 were determined on day 4 of both periods. Plasma samples were assayed by a high\u2010performance liquid chromatography\u2010ultraviolet method for nelfinavir and M8 concentrations, and noncompartmental pharmacokinetic analysis was performed by using analytical software. In the presence of omeprazole, nelfinavir area under the concentration\u2010time curve over the dosing interval (AUC<jats:sub>\u1e97<\/jats:sub>), maximum observed plasma concentration (C<jats:sub>max<\/jats:sub>), and minimum observed plasma concentration (C<jats:sub>min<\/jats:sub>) were reduced by an average of 36%, 37%, and 39%, respectively, relative to administration of nelfinavir alone. The AUC<jats:sub>\u1e97<\/jats:sub>, C<jats:sub>max<\/jats:sub>, and C<jats:sub>min<\/jats:sub> of M8 were reduced by an average of 92%, 89%, and 75%, respectively. The slopes of the terminal elimination phase of nelfinavir and M8 plasma concentration\u2010time curves were similar between treatments. Nelfinavir was well tolerated when administered alone and when coadministered with omeprazole.<\/jats:p><jats:p><jats:bold>Conclusion.<\/jats:bold> The observed reduction in the systemic exposure to both nelfinavir and its active metabolite M8 after coadministration with omeprazole could result in loss of virologic control and potential emergence of drug resistance. Hence, omeprazole should not be coadministered to patients taking nelfinavir.<\/jats:p>","DOI":"10.1592\/phco.28.1.42","type":"journal-article","created":{"date-parts":[[2007,12,21]],"date-time":"2007-12-21T13:26:01Z","timestamp":1198243561000},"page":"42-50","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Significant Decrease in Nelfinavir Systemic Exposure After Omeprazole Coadministration in Healthy Subjects"],"prefix":"10.1002","volume":"28","author":[{"given":"Annie F.","family":"Fang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bharat D.","family":"Damle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert R.","family":"LaBadie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Penelope H.","family":"Crownover","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Dial","family":"Hewlett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul W.","family":"Glue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,1,6]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.26.8.1111"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1089\/apc.2005.19.286"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200565150-00015"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200059030-00014"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.4.1086-1093.2001"},{"key":"e_1_2_1_7_2","unstructured":"LillibridgeJH LeeCA PithavalaYK et al.The role of polymorphic CYP2C19 in the metabolism of nelfinavir mesylate.Presented at the 12th annual meeting of the American Association of Pharmaceutical Scientists San Francisco CA November 1519 1998."},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.104.001743"},{"key":"e_1_2_1_9_2","first-page":"528","volume-title":"Physicians' Desk Reference","author":"Anonymous.","year":"1998"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199631010-00002"},{"key":"e_1_2_1_11_2","first-page":"853","article-title":"Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms","volume":"25","author":"Ko JW","year":"1997","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199815000-00025"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.26.3.341"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.26.4.511"},{"key":"e_1_2_1_15_2","unstructured":"Food and Drug Administration.BMS Dear Dr. letter. 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