{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T06:19:02Z","timestamp":1762409942369,"version":"3.40.5"},"reference-count":22,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T00:00:00Z","timestamp":1625702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R01DA\u2010023223"],"award-info":[{"award-number":["R01DA\u2010023223"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gamma hydroxybutyric acid (GHB) has been approved clinically to treat excessive daytime sleepiness and cataplexy in patients with narcolepsy, alcohol and opioid withdrawal, and as an anesthetic. The use of GHB clinically is limited due to its high abuse potential. The absorption, clearance and tissue uptake of GHB is mediated by proton\u2010dependent and sodium\u2010coupled monocarboxylate transporters (MCTs and SMCTs) and inhibition of these transporters may result in a change in GHB pharmacokinetics and pharmacodynamics. Previous studies have reported that non\u2010steroidal anti\u2010inflammatory drugs (NSAIDs) may inhibit these monocarboxylate transporters. Therefore, the purpose of this work was to analyze the interaction between GHB (at a dose of 600 mg\/kg i. v.) and the NSAID, diclofenac, by examining the effects of this drug on the in vivo pharmacokinetics and pharmacodynamics in rat studies. The pharmacodynamic effect evaluated was respiratory depression, a measure of toxicity observed by GHB at this dose. There was an improvement in the respiratory rate with diclofenac administration suggesting an effect of diclofenac on GHB toxicity. In vitro studies with rat blood brain endothelial cells (RBE4) that express MCT1 indicated that diclofenac can inhibit GHB transport with an IC<jats:sub>50<\/jats:sub> of 10.6 \u03bcM at pH 7.4. In vivo studies found a decrease in brain GHB concentrations and a decrease in the brain\u2010to\u2010plasma concentration ratio following diclofenac treatment. With this study we can conclude that diclofenac and potentially other NSAIDs can inhibit the transport of GHB into the brain, therefore decreasing GHB's pharmacodynamic effects and toxicity.<\/jats:p>","DOI":"10.1002\/bdd.2296","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T08:16:19Z","timestamp":1625127379000},"page":"351-358","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Drug\u2010drug interaction between diclofenac and gamma\u2010hydroxybutyric acid"],"prefix":"10.1002","volume":"42","author":[{"given":"Vivian","family":"Rodriguez\u2010Cruz","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical Sciences University at Buffalo State University of New York  Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianjing","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical Sciences University at Buffalo State University of New York  Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1127-7964","authenticated-orcid":false,"given":"Marilyn E.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical Sciences University at Buffalo State University of New York  Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,7,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/02791072.2014.921746"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00210.2018"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2009.04.012"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.109.027169"},{"volume-title":"Method of administration of Gamma Hydroxybutyrate with monocarboxylate transporters","year":"2013","author":"Eller M.","key":"e_1_2_7_6_1"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.165381"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.119.256503"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-006-0023-1"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-008-9035-6"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.113.206250"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.112.078154"},{"volume-title":"PubChem compound summary for CID 3033","year":"2021","author":"National Center for Biotechnology Information","key":"e_1_2_7_13_1"},{"volume-title":"PubChem compound summary for CID 10413, 4\u2010hydroxybutanoic acid","year":"2021","author":"National Center for Biotechnology Information","key":"e_1_2_7_14_1"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-4642(18)30133-0"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.3109\/03009747809097212"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.111.041749"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-013-0973-z"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389200033489398"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-014-1583-0"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.105965"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.107.014852"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2010.01.007"}],"container-title":["Biopharmaceutics &amp; 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