{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T06:04:04Z","timestamp":1776405844231,"version":"3.51.2"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2010,10,12]],"date-time":"2010-10-12T00:00:00Z","timestamp":1286841600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Psychiatr Scand"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:p>Davies SJC, Westin AA, Castberg I, Lewis G, Lennard MS, Taylor S, Spigset O. Characterisation of zuclopenthixol metabolism by <jats:italic>in vitro<\/jats:italic> and therapeutic drug monitoring studies.<\/jats:p><jats:p><jats:bold>Objective:\u2002<\/jats:bold> Zuclopenthixol pharmacokinetics is incompletely characterised. We investigated potential interactions mediated through cytochrome P450 enzymes.<\/jats:p><jats:p><jats:bold>Method:\u2002<\/jats:bold>  <jats:italic>In vitro<\/jats:italic>, we examined the impact of CYP2D6 and CYP3A4 inhibitors on zuclopenthixol metabolism in microsomes from six human livers. Subsequently, we compared dose\u2010corrected serum zuclopenthixol concentrations in 923 samples from a therapeutic drug monitoring database from patients prescribed oral (<jats:italic>n<\/jats:italic> = 490) or injected (<jats:italic>n<\/jats:italic> = 423) zuclopenthixol alone or with fluoxetine, paroxetine, levomepromazine or carbamazepine.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold>  <jats:italic>In vitro<\/jats:italic> fluoxetine, paroxetine, ketoconazole and quinidine all significantly inhibited zuclopenthixol metabolism. Ketoconazole and quinidine together abolished zuclopenthixol disappearance. Clinically, dose\u2010corrected oral zuclopenthixol serum concentrations increased significantly, after adjustment, by 93%, 78% and 46% during co\u2010treatment with fluoxetine, paroxetine and levomepromazine and decreased 67% with carbamazepine. Carbamazepine caused dose\u2010dependent reductions in the oral zuclopenthixol concentration\u2013dose ratio (<jats:italic>P<\/jats:italic> &lt; 0.001), fluoxetine (<jats:italic>P<\/jats:italic> &lt; 0.001) and paroxetine (<jats:italic>P<\/jats:italic> = 0.011) dose\u2010dependent increases and levomepromazine an increase related to its serum concentration (<jats:italic>P<\/jats:italic> &lt; 0.001). Results for injected zuclopenthixol were similar but not all reached statistical significance.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> The <jats:italic>In vitro<\/jats:italic> study suggests zuclopenthixol is metabolised primarily by CYP2D6 and CYP3A4. The clinical study supports this, demonstrating the impact of co\u2010prescribed inhibitors or inducers. Guidelines should incorporate these interactions noting the potential for zuclopenthixol\u2010related toxicity or treatment failure.<\/jats:p>","DOI":"10.1111\/j.1600-0447.2010.01619.x","type":"journal-article","created":{"date-parts":[[2010,10,12]],"date-time":"2010-10-12T07:00:24Z","timestamp":1286866824000},"page":"444-453","source":"Crossref","is-referenced-by-count":18,"title":["Characterisation of zuclopenthixol metabolism by <i>in vitro<\/i> and therapeutic drug monitoring studies"],"prefix":"10.1111","volume":"122","author":[{"given":"S. J. C.","family":"Davies","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. 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