{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T02:59:32Z","timestamp":1700189972096},"reference-count":27,"publisher":"Wiley","issue":"s1","license":[{"start":{"date-parts":[[2004,10,20]],"date-time":"2004-10-20T00:00:00Z","timestamp":1098230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2004,11]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>To investigate the effects of donepezil at steady state on the safety, tolerability and pharmacokinetics of a single dose of thioridazine, in healthy subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An open, two\u2010way, balanced crossover study, in 12 subjects (six men and six women) aged 19\u201341\u2003years. During both treatment periods, subjects received a single oral dose of 50\u2003mg thioridazine; in one period the thioridazine was given alone, and in the other period it was given together with the last of 15 daily, oral doses of donepezil 5\u2003mg. The \u2018washout\u2019 periods were 1\u2003week when thioridazine was given first, and 2\u2003weeks when thioridazine was given last. Plasma concentrations of thioridazine were measured after each dose, and pharmacokinetic parameters were determined. Interactions were tested by using an equivalence analysis in which thioridazine was the \u2018Reference\u2019 and thioridazine + donepezil the \u2018Test\u2019 regimen. Safety and tolerability were monitored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Donepezil had no marked effect on the pharmacokinetics of thioridazine, as judged by the equivalence analysis of AUC<jats:sub>0\u2013<jats:italic>t<\/jats:italic>n<\/jats:sub>, AUC<jats:sub>0\u2013\u221e<\/jats:sub>, <jats:italic>t<\/jats:italic><jats:sub>\u00bd<\/jats:sub> and <jats:italic>t<\/jats:italic><jats:sub>max<\/jats:sub>. <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> was very similar in the \u2018Test\u2019 and \u2018Reference\u2019 regimens, but the confidence intervals were too wide to confirm equivalence. Donepezil was well tolerated, whereas thioridazine was associated with light\u2010headedness, tiredness and postural hypotension, irrespective of whether or not donepezil was given concurrently.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Repeated dosing with donepezil, 5\u2003mg daily for 2\u2003weeks, had no significant effect on the safety, tolerability or pharmacokinetics of thioridazine. 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