{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T09:23:57Z","timestamp":1768296237626,"version":"3.49.0"},"reference-count":61,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,10,21]],"date-time":"2013-10-21T00:00:00Z","timestamp":1382313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To confirm by means of pentagastrin, a synthetic gastrin agonist, that netazepide is a gastrin\/<jats:styled-content style=\"fixed-case\">CCK<jats:sub>2<\/jats:sub><\/jats:styled-content>receptor antagonist in healthy subjects, and that antagonism persists during repeated dosing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We did two studies in which we infused pentagastrin (0.6\u2009\u03bcg\u2009kg<jats:sup>\u22121<\/jats:sup>\u2009h<jats:sup>\u22121<\/jats:sup>intravenously), aspirated gastric secretion and measured the volume,<jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\"><jats:roman>H<jats:sup>+<\/jats:sup><\/jats:roman><\/jats:styled-content>secretion rate of the gastric aspirate. First, we did a double\u2010blind, five\u2010way crossover study (<jats:italic>n<\/jats:italic>= 10) to assess the effect of single oral doses of netazepide (1, 5, 25 and 100\u2009mg) and placebo on the response to pentagastrin. Then, we did a single\u2010blind, placebo\u2010controlled study (<jats:italic>n<\/jats:italic>= 8) to assess the effect of the first and last oral doses of netazepide (100\u2009mg) twice daily for 13 doses on the response to pentagastrin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Netazepide was well tolerated. After placebo, pentagastrin increased the volume and<jats:styled-content style=\"fixed-case\"><jats:roman>H<jats:sup>+<\/jats:sup><\/jats:roman><\/jats:styled-content>secretion rate and reduced the<jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content>of gastric aspirate. Compared with placebo, single doses of netazepide caused dose\u2010dependent inhibition of the pentagastrin response (<jats:italic>P<\/jats:italic>&lt; 0.02); netazepide (100\u2009mg) abolished the response. After 13 doses, the reduction in volume and<jats:styled-content style=\"fixed-case\"><jats:roman>H<jats:sup>+<\/jats:sup><\/jats:roman><\/jats:styled-content>secretion rate persisted (<jats:italic>P<\/jats:italic>&lt; 0.001), but the<jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content>effect was mostly lost.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Netazepide is an orally active, potent, competitive antagonist of human gastrin\/<jats:styled-content style=\"fixed-case\">CCK<jats:sub>2<\/jats:sub><\/jats:styled-content>receptors. Antagonism is dose dependent and persists during repeated dosing, despite tolerance to the effect on<jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content>. Further studies are required to explain that tolerance. Netazepide is a tool to study the physiology and pharmacology of gastrin, and merits studies in patients to assess its potential to treat gastric acid\u2010related conditions and the trophic effects of hypergastrinaemia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12099","type":"journal-article","created":{"date-parts":[[2013,2,21]],"date-time":"2013-02-21T18:16:51Z","timestamp":1361470611000},"page":"689-698","source":"Crossref","is-referenced-by-count":21,"title":["Netazepide, a gastrin\/<scp>CCK<sub>2<\/sub><\/scp>receptor antagonist, causes dose\u2010dependent, persistent inhibition of the responses to pentagastrin in healthy subjects"],"prefix":"10.1111","volume":"76","author":[{"given":"Malcolm","family":"Boyce","sequence":"first","affiliation":[{"name":"Hammersmith Medicines Research Central Middlesex Hospital London NW10 7NS UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"Warrington","sequence":"additional","affiliation":[{"name":"Hammersmith Medicines Research Central Middlesex Hospital London NW10 7NS UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Black","sequence":"additional","affiliation":[{"name":"James Black Foundation Half Moon Lane Dulwich London SE24 9JE UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,10,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm960669"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.1997.110281000.x"},{"key":"e_1_2_8_4_1","first-page":"403","article-title":"Effects of YF476, a potent and selective gastrin\/CCK\u2010B receptor antagonist, on gastric acid secretion in beagle dogs with gastric fistula","volume":"48","author":"Takemoto Y","year":"1998","journal-title":"Arzneim Forsch"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01649_1.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2012.05143.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12095"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1997.tb00052.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1163\/156856002321544828"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703342"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704037"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-0115(02)00111-8"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgg156"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.03.027"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700462"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2010.01.009"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00134.2010"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.63.1.119"},{"key":"e_1_2_8_19_1","first-page":"684P","article-title":"Effect of repeated doses of YF476, a gastrin antagonist, on pentagastrin\u2010induced changes in volume, H+ content and pH of gastric aspirate in healthy subjects [abstract]","volume":"57","author":"Boyce M","year":"2004","journal-title":"Br J Clin Pharmacol"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.5694.458"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1570-0232(02)00118-6"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00102.2004"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1931.sp002822"},{"key":"e_1_2_8_24_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S0016-5085(70)80035-X","article-title":"Undissociated acidity of human gastric juice. Measurement and relationship to protein buffers","volume":"58","author":"Makhlouf G","year":"1970","journal-title":"Gastroenterology"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.18.3.208"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365516609087202"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI107226"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110969"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365529309098299"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(85)90454-8"},{"key":"e_1_2_8_31_1","doi-asserted-by":"crossref","first-page":"G188","DOI":"10.1152\/ajpgi.1985.248.2.G188","article-title":"Gastric H+ and HCO3\u2013 secretion in response to sham feeding in humans","volume":"11","author":"Feldman M","year":"1985","journal-title":"Gastrointest Liver Physiol"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.28.6.739"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01391739"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1989.tb08659.x"},{"key":"e_1_2_8_35_1","first-page":"829","article-title":"Measurement of gastric bicarbonate in the human stomach: different methods produce discordant results. Scand J","volume":"27","author":"Odes H","year":"1992","journal-title":"Gastroenterology"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-0115(01)00307-X"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161210790945904"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2006.036483"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.90340.2008"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1163\/156856005774423872"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-0238"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12576-008-0001-y"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)00908-9"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00348.2006"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOG.0b013e3282f01dbd"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1080\/003655299750025480"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00231110"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2006.03130.x"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004836-200107000-00008"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.03.058"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2010.81"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2006.03127.x"},{"issue":"1","key":"e_1_2_8_53_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.1365-2036.1990.tb00011.x","article-title":"Tolerance during 8 days of high\u2010dose H2\u2010blockade: placebo\u2010controlled studies of 24\u2010hour acidity and gastrin","volume":"4","author":"Smith J","year":"1990","journal-title":"Aliment Pharmacol Ther"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12090"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-302514a.97"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543776.11.3.445"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0773.2002.910602.x"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1993.185"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2362.1999.00424.x"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3223(94)00190-E"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004714-199512000-00007"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.11.026"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbcp.12099","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.12099","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T21:53:44Z","timestamp":1745963624000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.12099"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,21]]},"references-count":61,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2013,11]]}},"alternative-id":["10.1111\/bcp.12099"],"URL":"https:\/\/doi.org\/10.1111\/bcp.12099","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,21]]}}}