{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T13:22:30Z","timestamp":1772544150876,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,8,2]],"date-time":"2017-08-02T00:00:00Z","timestamp":1501632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:p>The oral bioavailability of diltiazem is very low due to rapid first pass metabolism in liver and intestine. The purpose of the study was to investigate the effect of gallic acid and ellagic acid on intestinal transport and oral bioavailability of diltiazem in rats. The intestinal transport and permeability of diltiazem was evaluated by<jats:italic>in vitro<\/jats:italic>non\u2010everted sac method and<jats:italic>in situ<\/jats:italic>single pass intestinal perfusion study. The oral pharmacokinetics was evaluated by conducting oral bioavailability study. The intestinal transport and apparent permeability of diltiazem were significantly enhanced in duodenum, jejunum, and ileum of gallic and ellagic acid\u2010treated groups. The effective permeability of diltiazem was significantly enhanced in ileum part of gallic and ellagic acid\u2010treated groups. When compared with control group, the presence of these two phytochemicals significantly enhanced the area under plasma concentration\u2010time curve and the peak plasma concentration of diltiazem (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>). Gallic acid and ellagic acid significantly increased the bioavailability of diltiazem due to the inhibition of both CYP3A\u2010mediated metabolism and P\u2010glycoprotein\u2010mediated efflux in the intestine and\/or liver. Based on these results, the clinical experiments are warranted for the confirmation to reduce the dose of diltiazem when concomitantly administered with these phytochemicals. Copyright \u00a9 2017 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/ptr.5873","type":"journal-article","created":{"date-parts":[[2017,8,2]],"date-time":"2017-08-02T10:00:40Z","timestamp":1501668040000},"page":"1441-1448","source":"Crossref","is-referenced-by-count":27,"title":["Enhanced Oral Bioavailability of Diltiazem by the Influence of Gallic Acid and Ellagic Acid in Male Wistar Rats: Involvement of CYP3A and P\u2010gp Inhibition"],"prefix":"10.1002","volume":"31","author":[{"given":"Bhargavi Latha","family":"Athukuri","sequence":"first","affiliation":[{"name":"DMPK and Clinical Pharmacology Division, Department of Pharmacology, University College of Pharmaceutical Sciences Kakatiya University Warangal 506 009 TS India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7145-1699","authenticated-orcid":false,"given":"Prasad","family":"Neerati","sequence":"additional","affiliation":[{"name":"DMPK and Clinical Pharmacology Division, Department of Pharmacology, University College of Pharmaceutical Sciences Kakatiya University Warangal 506 009 TS India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,8,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.39.1.361"},{"issue":"4","key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1515\/dmpt-2016-0029","article-title":"Enhanced oral bioavailability of metoprolol with gallic acid and ellagic acid in male Wistar rats: involvement of CYP2D6 inhibition","volume":"31","author":"Athukuri BL","year":"2016","journal-title":"Drug Metab Pers Ther"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-3659(95)00147-6"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-198529050-00001"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2005.05.011"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2710.2009.01096.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-003-1996-9"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200038010-00003"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2010.05.012"},{"key":"e_1_2_7_11_1","first-page":"200","article-title":"Interactions between herbal and conventional medicines: the role of cytochrome p450 enzymes and p\u2010glycoprotein","volume":"2","author":"Elizabeth MW","year":"2006","journal-title":"Pharmacologyonline"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470319444.ch11"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2004.08.018"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-014-0238-1"},{"key":"e_1_2_7_15_1","first-page":"338","volume-title":"Metabolic Drug Interactions","author":"Jones DR","year":"2000"},{"issue":"5","key":"e_1_2_7_16_1","first-page":"790","article-title":"Studies of the intestinal transfer of coumarin and 7\u2010hydroxycoumarin across guinea pig and rat small intestine","volume":"31","author":"Kaul Sand Ritschel WA","year":"1981","journal-title":"Arzneimittelforschung"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2009.10.041"},{"key":"e_1_2_7_18_1","first-page":"115","article-title":"Inhibition of platelet aggregation by diltiazem. 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