{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T06:54:30Z","timestamp":1779346470084,"version":"3.51.4"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2001,12,24]],"date-time":"2001-12-24T00:00:00Z","timestamp":1009152000000},"content-version":"vor","delay-in-days":632,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2000,4]]},"abstract":"<jats:p><jats:bold><jats:italic>Aims<\/jats:italic><\/jats:bold>\u2002To examine the potency of ticlopidine (TCL) as an inhibitor of cytochrome P450s (CYP450s)<jats:italic>in vitro<\/jats:italic>using human liver microsomes (HLMs) and recombinant human CYP450s.<\/jats:p><jats:p><jats:bold><jats:italic>Methods<\/jats:italic><\/jats:bold>\u2002Isoform\u2010specific substrate probes of CYP1A2, 2C19, 2C9, 2D6, 2E1 and 3A4 were incubated in HLMs or recombinant CYPs with or without TCL. Preliminary data were generated to simulate an appropriate range of substrate and inhibitor concentrations to construct Dixon plots. In order to estimate accurately inhibition constants (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>values) of TCL and determine the type of inhibition, data from experiments with three different HLMs for each isoform were fitted to relevant nonlinear regression enzyme inhibition models by WinNonlin.<\/jats:p><jats:p><jats:bold><jats:italic>Results<\/jats:italic><\/jats:bold>\u2002TCL was a potent, competitive inhibitor of CYP2C19 (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>\u2003=\u20031.2\u2003\u00b1\u20030.5\u2003\u00b5<jats:sc>m<\/jats:sc>) and of CYP2D6 (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>\u2003=\u20033.4\u2003\u00b1\u20030.3\u2003\u00b5<jats:sc>m<\/jats:sc>). These<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>values fell within the therapeutic steady\u2010state plasma concentrations of TCL (1\u20133\u2003\u00b5<jats:sc>m<\/jats:sc>). TCL was also a moderate inhibitor of CYP1A2 (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>\u2003=\u200349\u2003\u00b1\u200319\u2003\u00b5<jats:sc>m<\/jats:sc>) and a weak inhibitor of CYP2C9 (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>\u2003&gt;\u200375\u2003\u00b5<jats:sc>m<\/jats:sc>), but its effect on the activities of CYP2E1 (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>\u2003=\u2003584\u2003\u00b1\u200348\u2003\u00b5<jats:sc>m<\/jats:sc>) and CYP3A (&gt;\u20031000\u2003\u00b5<jats:sc>m<\/jats:sc>) was marginal.<\/jats:p><jats:p><jats:bold><jats:italic>Conclusions<\/jats:italic><\/jats:bold>\u2002TCL appears to be a broad\u2010spectrum inhibitor of the CYP isoforms, but clinically significant adverse drug interactions are most likely with drugs that are substrates of CYP2C19 or CYP2D6.<\/jats:p>","DOI":"10.1046\/j.1365-2125.2000.00175.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T04:37:43Z","timestamp":1047357463000},"page":"343-351","source":"Crossref","is-referenced-by-count":87,"title":["<i>In vitro<\/i>inhibition of the cytochrome P450 (CYP450) system by the antiplatelet drug ticlopidine: potent effect on CYP2C19 and CYP2D6"],"prefix":"10.1111","volume":"49","author":[{"given":"Jae Wook","family":"Ko,","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeruesenay","family":"Desta,","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia V","family":"Soukhova,","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Tracy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David 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