{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T19:05:47Z","timestamp":1776366347881,"version":"3.51.2"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,4,22]],"date-time":"2015-04-22T00:00:00Z","timestamp":1429660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS076665"],"award-info":[{"award-number":["R01 NS076665"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K01 NS050309"],"award-info":[{"award-number":["K01 NS050309"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007249","name":"University of Minnesota","doi-asserted-by":"crossref","award":["Academic Health Center"],"award-info":[{"award-number":["Academic Health Center"]}],"id":[{"id":"10.13039\/100007249","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2015,5]]},"abstract":"Aims<\/jats:title>The aim was to develop a quantitative approach that characterizes the magnitude of and variability in phonemic generative fluency scores as measured by the C<\/jats:styled-content>ontrolled O<\/jats:styled-content>ral W<\/jats:styled-content>ord A<\/jats:styled-content>ssociation (COWA<\/jats:styled-content>) test in healthy volunteers after administration of an oral and a novel intravenous (IV<\/jats:styled-content>) formulation of topiramate (TPM<\/jats:styled-content>).<\/jats:p><\/jats:sec>Methods<\/jats:title>Nonlinear mixed\u2010effects modelling was used to describe the plasma TPM<\/jats:styled-content> concentrations resulting from oral or IV<\/jats:styled-content> administration. A pharmacokinetic\u2013pharmacodynamic (PK<\/jats:styled-content>\u2010PD<\/jats:styled-content>) model was developed sequentially to characterize the effect of TPM<\/jats:styled-content> concentrations on COWA<\/jats:styled-content> with different distributional assumptions.<\/jats:p><\/jats:sec>Results<\/jats:title>Topiramate was rapidly absorbed, with a median time to maximal concentration of 1\u2009h and an oral bioavailability of \u223c100%. Baseline COWA<\/jats:styled-content> score increased by an average of 12% after the third administration on drug\u2010free sessions. An exponential model described the decline of COWA<\/jats:styled-content> scores, which decreased by 14.5% for each 1\u2009mg\u2009l\u22121<\/jats:sup> increase in TPM<\/jats:styled-content> concentration. The COWA<\/jats:styled-content> scores were described equally well by both continuous normal and Poisson distributions.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>This analysis quantified the effect of TPM<\/jats:styled-content> exposure on generative verbal fluency as measured by COWA<\/jats:styled-content>. Repetitive administration of COWA<\/jats:styled-content> resulted in a better performance, possibly due to a learning effect. The model predicts a 27% reduction in the COWA<\/jats:styled-content> score at the average observed maximal plasma concentration after a 100\u2009mg dose of TPM<\/jats:styled-content>. The single\u2010dose administration of relatively low TPM<\/jats:styled-content> doses and narrow range of resultant concentrations in our study were limitations to investigating the PK<\/jats:styled-content>\u2010PD<\/jats:styled-content> relationship at higher TPM<\/jats:styled-content> exposures. Hence, the findings may not be readily generalized to the broader patient population.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12556","type":"journal-article","created":{"date-parts":[[2014,11,18]],"date-time":"2014-11-18T07:25:54Z","timestamp":1416295554000},"page":"820-830","source":"Crossref","is-referenced-by-count":15,"title":["Pharmacokinetic\u2013pharmacodynamic modelling of intravenous and oral topiramate and its effect on phonemic fluency in adult healthy volunteers"],"prefix":"10.1111","volume":"79","author":[{"given":"Ghada F.","family":"Ahmed","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology College of Pharmacy University of Minnesota Minneapolis MN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan E.","family":"Marino","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology College of Pharmacy University of Minnesota Minneapolis MN USA"},{"name":"Center for Clinical and Cognitive Neuropharmacology College of Pharmacy University of Minnesota Minneapolis MN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard C.","family":"Brundage","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology College of Pharmacy University of Minnesota Minneapolis MN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serguei V. 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