{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T07:50:07Z","timestamp":1767772207333,"version":"3.37.3"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T00:00:00Z","timestamp":1602806400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T00:00:00Z","timestamp":1602806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Drug Metab Pharmacokinet"],"published-print":{"date-parts":[[2021,1]]},"DOI":"10.1007\/s13318-020-00649-x","type":"journal-article","created":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T05:02:39Z","timestamp":1602824559000},"page":"41-51","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Physiologically Based Pharmacokinetic Modeling Approach to Identify the Drug\u2013Drug Interaction Mechanism of Nifedipine and a Proton Pump Inhibitor, Omeprazole"],"prefix":"10.1007","volume":"46","author":[{"given":"Maxime","family":"Le Merdy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Liang","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dajun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhanglin","family":"Ni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sue-Chih","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9968-0197","authenticated-orcid":false,"given":"Andrew","family":"Babiskin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,10,16]]},"reference":[{"key":"649_CR1","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1124\/dmd.109.026716","volume":"37","author":"SW Grimm","year":"2009","unstructured":"Grimm SW, Einolf HJ, Hall SD, He K, Lim H-K, Ling K-HJ, et al. The conduct of in vitro studies to address time-dependent inhibition of drug-metabolizing enzymes: a perspective of the pharmaceutical research and manufacturers of America. Drug Metab Dispos Biol Fate Chem. 2009;37:1355\u201370.","journal-title":"Drug Metab Dispos Biol Fate Chem."},{"key":"649_CR2","doi-asserted-by":"publisher","first-page":"3289","DOI":"10.1002\/jps.24560","volume":"104","author":"J Gajendran","year":"2015","unstructured":"Gajendran J, Kr\u00e4mer J, Shah VP, Langguth P, Polli J, Mehta M, et al. Biowaiver monographs for immediate-release solid oral dosage forms: nifedipine. J Pharm Sci. 2015;104:3289\u201398.","journal-title":"J Pharm Sci"},{"key":"649_CR3","unstructured":"US. FDA. PROCARDIA\u00ae (nifedipine) CAPSULES For Oral Use [Internet]. 2013. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2013\/018482s051lbl.pdf. Accessed 20 Aug 2020."},{"key":"649_CR4","doi-asserted-by":"publisher","first-page":"5051","DOI":"10.1016\/S0021-9258(19)89213-X","volume":"261","author":"FP Guengerich","year":"1986","unstructured":"Guengerich FP, Martin MV, Beaune PH, Kremers P, Wolff T, Waxman DJ. Characterization of rat and human liver microsomal cytochrome P-450 forms involved in nifedipine oxidation, a prototype for genetic polymorphism in oxidative drug metabolism. J Biol Chem. 1986;261:5051\u201360.","journal-title":"J Biol Chem"},{"key":"649_CR5","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.1124\/dmd.111.041293","volume":"39","author":"BW Ogilvie","year":"2011","unstructured":"Ogilvie BW, Yerino P, Kazmi F, Buckley DB, Rostami-Hodjegan A, Paris BL, et al. The proton pump inhibitor, omeprazole, but not lansoprazole or pantoprazole, is a metabolism-dependent inhibitor of CYP2C19: implications for coadministration with clopidogrel. Drug Metab Dispos Biol Fate Chem. 2011;39:2020\u201333.","journal-title":"Drug Metab Dispos Biol Fate Chem"},{"key":"649_CR6","first-page":"853","volume":"25","author":"JW Ko","year":"1997","unstructured":"Ko JW, Sukhova N, Thacker D, Chen P, Flockhart DA. Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms. Drug Metab Dispos Biol Fate Chem. 1997;25:853\u201362.","journal-title":"Drug Metab Dispos Biol Fate Chem"},{"key":"649_CR7","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1124\/dmd.32.8.821","volume":"32","author":"X-Q Li","year":"2004","unstructured":"Li X-Q, Andersson TB, Ahlstr\u00f6m M, Weidolf L. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos Biol Fate Chem. 2004;32:821\u20137.","journal-title":"Drug Metab Dispos Biol Fate Chem"},{"key":"649_CR8","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.1124\/dmd.113.051722","volume":"41","author":"Y Shirasaka","year":"2013","unstructured":"Shirasaka Y, Sager JE, Lutz JD, Davis C, Isoherranen N. Inhibition of CYP2C19 and CYP3A4 by omeprazole metabolites and their contribution to drug-drug interactions. Drug Metab Dispos Biol Fate Chem. 2013;41:1414\u201324.","journal-title":"Drug Metab Dispos Biol Fate Chem"},{"key":"649_CR9","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1007\/BF00266355","volume":"42","author":"PA Soons","year":"1992","unstructured":"Soons PA, van den Berg G, Danhof M, van Brummelen P, Jansen JB, Lamers CB, et al. Influence of single- and multiple-dose omeprazole treatment on nifedipine pharmacokinetics and effects in healthy subjects. Eur J Clin Pharmacol. 1992;42:319\u201324.","journal-title":"Eur J Clin Pharmacol"},{"key":"649_CR10","unstructured":"US FDA. Evaluation of formulation dependence of drug-drug interaction with proton pump inhibitors (PPIs) for oral extended-release drug products; Contract #: HHSF223201610004I [Internet]. https:\/\/www.fda.gov\/industry\/generic-drug-user-fee-amendments\/fy2016-regulatory-science-report-modified-release-drug-products-therapeutic-equivalence-between. Accessed 20 Aug 2020."},{"key":"649_CR11","doi-asserted-by":"publisher","first-page":"509","DOI":"10.2165\/11531320-000000000-00000","volume":"49","author":"R Ogawa","year":"2010","unstructured":"Ogawa R, Echizen H. Drug-drug interaction profiles of proton pump inhibitors. Clin Pharmacokinet. 2010;49:509\u201333.","journal-title":"Clin Pharmacokinet"},{"key":"649_CR12","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/s40264-014-0144-0","volume":"37","author":"R-S Wedemeyer","year":"2014","unstructured":"Wedemeyer R-S, Blume H. Pharmacokinetic drug interaction profiles of proton pump inhibitors: an update. Drug Saf. 2014;37:201\u201311.","journal-title":"Drug Saf"},{"key":"649_CR13","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.1007\/s11095-013-1293-z","volume":"31","author":"F Wu","year":"2014","unstructured":"Wu F, Gaohua L, Zhao P, Jamei M, Huang S-M, Bashaw ED, et al. Predicting nonlinear pharmacokinetics of omeprazole enantiomers and racemic drug using physiologically based pharmacokinetic modeling and simulation: application to predict drug\/genetic interactions. Pharm Res. 2014;31:1919\u201329.","journal-title":"Pharm Res"},{"key":"649_CR14","first-page":"240","volume":"57","author":"N Patel","year":"2014","unstructured":"Patel N, Polak S, Jamei M, Rostami-Hodjegan A, Turner DB. Quantitative prediction of formulation-specific food effects and their population variability from in vitro data with the physiologically-based ADAM model: a case study using the BCS\/BDDCS Class II drug nifedipine. Eur J Pharm Sci Off J Eur Fed Pharm Sci. 2014;57:240\u20139.","journal-title":"Eur J Pharm Sci Off J Eur Fed Pharm Sci"},{"key":"649_CR15","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.ijpharm.2015.03.008","volume":"485","author":"F Liu","year":"2015","unstructured":"Liu F, Shokrollahi H. In vitro dissolution of proton-pump inhibitor products intended for paediatric and geriatric use in physiological bicarbonate buffer. Int J Pharm. 2015;485:152\u20139.","journal-title":"Int J Pharm"},{"key":"649_CR16","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1007\/s00228-004-0841-1","volume":"60","author":"M Hassan-Alin","year":"2005","unstructured":"Hassan-Alin M, Andersson T, Niazi M, R\u00f6hss K. A pharmacokinetic study comparing single and repeated oral doses of 20 mg and 40 mg omeprazole and its two optical isomers, S-omeprazole (esomeprazole) and R-omeprazole, in healthy subjects. Eur J Clin Pharmacol. 2005;60:779\u201384.","journal-title":"Eur J Clin Pharmacol"},{"key":"649_CR17","doi-asserted-by":"publisher","first-page":"263","DOI":"10.2165\/00044011-200828050-00001","volume":"28","author":"T Andersson","year":"2008","unstructured":"Andersson T, Weidolf L. Stereoselective disposition of proton pump inhibitors. Clin Drug Investig. 2008;28:263\u201379.","journal-title":"Clin Drug Investig"},{"key":"649_CR18","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1038\/clpt.2011.305","volume":"91","author":"MLT Vieira","year":"2012","unstructured":"Vieira MLT, Zhao P, Berglund EG, Reynolds KS, Zhang L, Lesko LJ, et al. Predicting drug interaction potential with a physiologically based pharmacokinetic model: a case study of telithromycin, a time-dependent CYP3A inhibitor. Clin Pharmacol Ther. 2012;91:700\u20138.","journal-title":"Clin Pharmacol Ther"},{"key":"649_CR19","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/S0016-5085(85)80133-5","volume":"88","author":"PJ Prichard","year":"1985","unstructured":"Prichard PJ, Yeomans ND, Mihaly GW, Jones DB, Buckle PJ, Smallwood RA, et al. Omeprazole: a study of its inhibition of gastric pH and oral pharmacokinetics after morning or evening dosage. Gastroenterology. 1985;88:64\u20139.","journal-title":"Gastroenterology"},{"key":"649_CR20","doi-asserted-by":"crossref","unstructured":"Ali SL. Nifedpine. In: Florey K, Al-Badr AA, Forcier GA, Brittain HG, Grady LT, editors. Anal Profiles Drug Subst. New York: Academic Press; 1990. pp. 221\u201388. https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0099542808606747. Accessed 28 May 2019.","DOI":"10.1016\/S0099-5428(08)60674-7"},{"key":"649_CR21","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1007\/s40262-018-0635-8","volume":"57","author":"C-H Hsueh","year":"2018","unstructured":"Hsueh C-H, Hsu V, Pan Y, Zhao P. Predictive performance of physiologically-based pharmacokinetic models in predicting drug-drug interactions involving enzyme modulation. Clin Pharmacokinet. 2018;57:1337\u2013466.","journal-title":"Clin Pharmacokinet"},{"key":"649_CR22","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1007\/s12272-017-0976-0","volume":"40","author":"JS Min","year":"2017","unstructured":"Min JS, Bae SK. Prediction of drug-drug interaction potential using physiologically based pharmacokinetic modeling. Arch Pharm Res. 2017;40:1356\u201379.","journal-title":"Arch Pharm Res"},{"key":"649_CR23","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/j.apsb.2016.04.004","volume":"6","author":"X Zhuang","year":"2016","unstructured":"Zhuang X, Lu C. PBPK modeling and simulation in drug research and development. Acta Pharm Sin B. 2016;6:430\u201340.","journal-title":"Acta Pharm Sin B"},{"key":"649_CR24","unstructured":"US. FDA. In vitro metabolism- and transporter-mediated drug-drug interaction studies guidance for industry [Internet]. 2017. https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/vitro-metabolism-and-transporter-mediated-drug-drug-interaction-studies-guidance-industry. Accessed 20 Aug 2020."},{"key":"649_CR25","unstructured":"US. FDA. Clinical drug interaction studies\u2014study design, data analysis, and clinical implications guidance for industry [Internet]. 2017. https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/clinical-drug-interaction-studies-study-design-data-analysis-and-clinical-implications-guidance. Accessed 20 Aug 2020."},{"key":"649_CR26","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.xphs.2018.10.033","volume":"108","author":"M Grimstein","year":"2019","unstructured":"Grimstein M, Yang Y, Zhang X, Grillo J, Huang S-M, Zineh I, et al. Physiologically based pharmacokinetic modeling in regulatory science: an update from the U.S. food and drug administration\u2019s office of clinical pharmacology. J Pharm Sci. 2019;108:21\u20135.","journal-title":"J Pharm Sci."},{"key":"649_CR27","unstructured":"Zhao P. \u201cTowards consistent regulatory assessment of physiologically-based pharmacokinetic modeling to support dosing recommendations.\u201d FDA pharmaceutical science and clinical pharmacology advisory committee meeting, 15 March 2017, Washington, DC. Presentation. 2017. https:\/\/www.fda.gov\/media\/104616\/download. Accessed 20 Aug 2020."},{"key":"649_CR28","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/BF00614196","volume":"30","author":"J Lobo","year":"1986","unstructured":"Lobo J, Jack DB, Kendall MJ. The intra- and inter-subject variability of nifedipine pharmacokinetics in young volunteers. Eur J Clin Pharmacol. 1986;30:57\u201360.","journal-title":"Eur J Clin Pharmacol"},{"key":"649_CR29","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1177\/0091270009357431","volume":"50","author":"ET Overton","year":"2010","unstructured":"Overton ET, Tschampa JM, Klebert M, Royal M, Rodriguez M, Spitz T, et al. The effect of acid reduction with a proton pump inhibitor on the pharmacokinetics of lopinavir or ritonavir in HIV-infected patients on lopinavir\/ritonavir-based therapy. J Clin Pharmacol. 2010;50:1050\u20135.","journal-title":"J Clin Pharmacol"},{"issue":"Suppl 2","key":"649_CR30","doi-asserted-by":"publisher","first-page":"53","DOI":"10.2165\/00003088-199937002-00006","volume":"37","author":"A Suri","year":"1999","unstructured":"Suri A, Bramer SL. Effect of omeprazole on the metabolism of cilostazol. Clin Pharmacokinet. 1999;37(Suppl 2):53\u20139.","journal-title":"Clin Pharmacokinet"},{"key":"649_CR31","unstructured":"Dean L. Omeprazole therapy and CYP2C19 genotype. In: Pratt V, McLeod H, Rubinstein W, Dean L, Kattman B, Malheiro A, editors. Med Genet Summ [Internet]. Bethesda (MD): National center for biotechnology information (US); 2012. https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK100895\/. Accessed 28 May 2019"},{"key":"649_CR32","doi-asserted-by":"publisher","first-page":"411","DOI":"10.2165\/00003088-200140060-00003","volume":"40","author":"T Andersson","year":"2001","unstructured":"Andersson T, Hassan-Alin M, Hasselgren G, R\u00f6hss K, Weidolf L. Pharmacokinetic studies with esomeprazole, the (S)-isomer of omeprazole. Clin Pharmacokinet. 2001;40:411\u201326.","journal-title":"Clin Pharmacokinet"},{"key":"649_CR33","unstructured":"US. FDA. Clinical pharmacology review, application number: 21-153\/21-154 [Internet]. 2000. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2001\/21154_nexium_biopharmr_p1.pdf. Accessed 20 Aug 2020."},{"key":"649_CR34","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/s00228-006-0251-7","volume":"63","author":"T Uno","year":"2007","unstructured":"Uno T, Niioka T, Hayakari M, Yasui-Furukori N, Sugawara K, Tateishi T. Absolute bioavailability and metabolism of omeprazole in relation to CYP2C19 genotypes following single intravenous and oral administrations. Eur J Clin Pharmacol. 2007;63:143\u20139.","journal-title":"Eur J Clin Pharmacol"},{"key":"649_CR35","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1248\/bpb.25.923","volume":"25","author":"T Kita","year":"2002","unstructured":"Kita T, Sakaeda T, Aoyama N, Sakai T, Kawahara Y, Kasuga M, et al. Optimal dose of omeprazole for CYP2C19 extensive metabolizers in anti-Helicobacter pylori therapy: pharmacokinetic considerations. Biol Pharm Bull. 2002;25:923\u20137.","journal-title":"Biol Pharm Bull"}],"container-title":["European Journal of Drug Metabolism and Pharmacokinetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13318-020-00649-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13318-020-00649-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13318-020-00649-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,16]],"date-time":"2021-10-16T21:02:30Z","timestamp":1634418150000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13318-020-00649-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,16]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["649"],"URL":"https:\/\/doi.org\/10.1007\/s13318-020-00649-x","relation":{},"ISSN":["0378-7966","2107-0180"],"issn-type":[{"type":"print","value":"0378-7966"},{"type":"electronic","value":"2107-0180"}],"subject":[],"published":{"date-parts":[[2020,10,16]]},"assertion":[{"value":"16 October 2020","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"No source of funding was used to conduct this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"All authors reported no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"Not applicable.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of Data and Materials"}},{"value":"Not applicable.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code Availability"}},{"value":"This article reflects the views of the authors and should not be construed to represent FDA\u2019s views or policies.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclaimer"}},{"value":"MLM: modeling strategy development, modeling work and manuscript writing. M-LT: modeling work and manuscript writing. DS: modeling strategy development and manuscript editing. ZN: modeling strategy development and manuscript editing. S-CL: modeling strategy development and manuscript editing. AB: modeling strategy development and manuscript writing. LZ: modeling strategy development and manuscript editing.","order":10,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author Contributions"}}]}}