{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T23:30:25Z","timestamp":1777937425026,"version":"3.51.4"},"reference-count":0,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2003,10,2]],"date-time":"2003-10-02T00:00:00Z","timestamp":1065052800000},"content-version":"vor","delay-in-days":2375,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[1997,4]]},"abstract":"<jats:p>\n\t\t\t\t\t\t<jats:italic>Aims<\/jats:italic> Triazolam, a triazolobenzodiazepine hypnotic agent, is metabolized by CYP3A4. Diltiazem is an inhibitor of this isozyme. The aim of this study was to determine if diltiazem affects plasma concentrations of triazolam in humans.<\/jats:p><jats:p>\n\t\t\t\t\t\t<jats:italic>Methods<\/jats:italic> We investigated the interaction between triazolam and diltiazem in a randomized, three\u2010phase crossover study. Seven healthy male volunteers received orally either a single 0.25\u2003mg dose of triazolam, a 0.25\u2003mg dose of triazolam after a 3\u2010day treatment of diltiazem (180\u2003mg day<jats:sup>\u22121<\/jats:sup>), or a placebo. Plasma samples were collected to determine triazolam concentration over a 24\u2003h period. The pharmacodynamic effects of triazolam were investigated using the peak saccadic velocity of eye movements (PSV), electroencephalogram (EEG), and visual analogue scale (VAS) through 8\u2003h.<\/jats:p><jats:p>\n\t\t\t\t\t\t<jats:italic>Results<\/jats:italic> Diltiazem pretreatment significantly increased the area under the triazolam concentration\u2010time curve (8.0\u00b12.4 to 18.2\u00b13.1\u2003ng\u2003ml<jats:sup>\u22121<\/jats:sup>\u2003h; <jats:italic>P<\/jats:italic>&lt;0.001; mean\u00b1s.d.). Peak triazolam concentration was increased (2.1\u00b10.7 to 3.6\u00b11.0\u2003ng\u2003ml<jats:sup>\u22121<\/jats:sup>, <jats:italic>P<\/jats:italic>&lt;0.05) and the elimination half\u2010life prolonged (4.1\u00b12.1 to 7.6\u00b11.9\u2003h; <jats:italic>P<\/jats:italic>&lt;0.01). The PSV, EEG, and VAS of the triazolam plus diltiazem group revealed significant differences from the triazolam alone group or the control placebo group.<\/jats:p><jats:p>\n\t\t\t\t\t\t<jats:italic>Conclusions<\/jats:italic> Diltiazem markedly affects the pharmacokinetics of triazolam and increases the intensity of its sedative effects. Inhibition of CYP3A isozyme by diltiazem may explain the observed pharmacokinetic interaction. Therefore, triazolam should be avoided when patients are using diltiazem.<\/jats:p>","DOI":"10.1046\/j.1365-2125.1997.00580.x","type":"journal-article","created":{"date-parts":[[2003,10,14]],"date-time":"2003-10-14T16:49:57Z","timestamp":1066150197000},"page":"367-372","source":"Crossref","is-referenced-by-count":27,"title":["Enhanced effect of triazolam with diltiazem"],"prefix":"10.1111","volume":"43","author":[{"given":"Kazuhiro","family":"Kosuge","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiko","family":"Nishimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiko","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuo","family":"Umemura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuyoshi","family":"Nakashima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoichi","family":"Ohashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,10,2]]},"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1365-2125.1997.00580.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1365-2125.1997.00580.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1046\/j.1365-2125.1997.00580.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T12:23:57Z","timestamp":1698409437000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1046\/j.1365-2125.1997.00580.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,4]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1997,4]]}},"alternative-id":["10.1046\/j.1365-2125.1997.00580.x"],"URL":"https:\/\/doi.org\/10.1046\/j.1365-2125.1997.00580.x","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,4]]}}}