{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T20:00:53Z","timestamp":1760299253640,"version":"3.41.0"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,1,25]],"date-time":"2016-01-25T00:00:00Z","timestamp":1453680000000},"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":[[2016,4]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Patients receiving lamotrigine therapy frequently use paracetamol concomitantly. While one study suggests a possible, clinically relevant drug\u2013drug interaction, practical recommendations of the concomitant use are inconsistent. We performed a systematic pharmacokinetic study in healthy volunteers to quantify the effect of 4\u00a0day treatment with paracetamol on the metabolism of steady\u2010state lamotrigine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twelve healthy, male volunteers participated in an open label, sequential interaction study. Lamotrigine was titrated to steady\u2010state (100\u00a0mg daily) over 36\u00a0days, and blood and urine sampling was performed in a non\u2010randomized order with and without paracetamol (1\u00a0g four times daily). The primary endpoint was change in steady\u2010state area under the plasma concentration\u2013time curve of lamotrigine. Secondary endpoints were changes in total apparent oral clearance, renal clearance, trough concentration of lamotrigine and formation clearance of lamotrigine glucuronide conjugates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Co\u2010administration of lamotrigine and paracetamol decreased the steady\u2010state area under the plasma concentration\u2013time curve of lamotrigine by 20% (95% CI 10%, 25%;<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) from 166 to 127\u00a0\u03bcmol\u00a0l<jats:sup>\u20131<\/jats:sup>. Concomitant administration of paracetamol increased the formation clearance of lamotrigine glucuronide conjugates by 45% (95% CI 18%, 79%,<jats:italic>P<\/jats:italic>\u00a0=\u00a00.005) from 1.7 to 2.8\u00a0l\u00a0h<jats:sup>\u20131<\/jats:sup>, while the trough value of lamotrigine was reduced by 25% (95% CI 12%, 36%,<jats:italic>P<\/jats:italic>\u00a0=\u00a00.003) from 5.3 to 3.9 \u03bcmol\u00a0l<jats:sup>\u20131<\/jats:sup>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Paracetamol statistically significantly induced steady\u2010state lamotrigine glucuronidation, resulting in a 20% decrease in total systemic exposure and a 25% decrease in trough value of lamotrigine. This interaction may be of clinical relevance in some patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12840","type":"journal-article","created":{"date-parts":[[2015,11,20]],"date-time":"2015-11-20T22:17:08Z","timestamp":1448057828000},"page":"735-741","source":"Crossref","is-referenced-by-count":16,"title":["Paracetamol decreases steady\u2010state exposure to lamotrigine by induction of glucuronidation in healthy subjects"],"prefix":"10.1111","volume":"81","author":[{"given":"Sandra","family":"Gastrup","sequence":"first","affiliation":[{"name":"Clinical Pharmacology, Department of Public Health University of Southern Denmark Odense"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tore Bjerregaard","family":"Stage","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Department of Public Health University of Southern Denmark Odense"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Palle Bach Nielsen","family":"Fruekilde","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Pharmacology Odense University Hospital Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per","family":"Damkier","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Department of Public Health University of Southern Denmark Odense"},{"name":"Department of Clinical Chemistry and Pharmacology Odense University Hospital Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,1,25]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"1909","article-title":"Therapeutic drug monitoring of the newer anti\u2010epilepsy medications","volume":"3","author":"Krasowski MD","year":"2010","journal-title":"Pharm Basel Switz"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2005.463007.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1990.162"},{"key":"e_1_2_9_5_1","unstructured":"Lamotrigine\u2010acetaminophen. 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