{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T23:07:25Z","timestamp":1776294445873,"version":"3.50.1"},"reference-count":55,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,7,8]],"date-time":"2018-07-08T00:00:00Z","timestamp":1531008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Croatian Agency for Medicinal Products and Medical Devices"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To investigate the impact of glucuronidation enzyme (<jats:italic>UGT1A4*3 142T&gt;G, UGT1A4*2 70C&gt;A, UGT2B7\u2009\u2013161C&gt;T<\/jats:italic>) and transporter (<jats:italic>MDR1\/ABCB1 1236C&gt;T, ABCG2 421C&gt;A<\/jats:italic>) polymorphisms on steady\u2010state disposition of lamotrigine and on the lamotrigine\u2013valproate interaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adults with epilepsy on lamotrigine monotherapy (<jats:italic>n\u00a0=<\/jats:italic>\u00a0131) or lamotrigine + valproate treatment (<jats:italic>n\u00a0=<\/jats:italic>\u00a074) were genotyped and steady\u2010state lamotrigine and valproate morning troughs were determined as a part of routine therapeutic drug monitoring.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No effect of<jats:italic>UGT<\/jats:italic>and<jats:italic>MDR1\/ABCB1<\/jats:italic>polymorphisms was observed. In the entire cohort,<jats:italic>ABCG2 421A<\/jats:italic>allele had no effect however an interaction between the variant allele and valproate was observed: (i) in lamotrigine\u2010only patients, variant allele (<jats:italic>vs<\/jats:italic>. wild type homozygosity) was independently (adjustments: age, sex, body mass index, lamotrigine dose, other polymorphisms) associated with mildly lower lamotrigine troughs [geometric means ratio (GMR)\u00a0=\u00a00.76, 95% confidence interval (CI) 0.59\u20130.98], whereas in lamotrigine + valproate patients it was associated with higher troughs (GMR\u00a0=\u00a01.72, 95%CI 1.14\u20132.62); (ii) valproate cotreatment was overall associated with markedly higher troughs<jats:italic>vs<\/jats:italic>. lamotrigine monotherapy (GMR\u00a0=\u00a03.49, 95%CI 2.73\u20134.44), but more so in variant allele carriers (GMR\u00a0=\u00a05.24, 95%CI 3.38\u20138.15) than in wild type homozygotes (GMR\u00a0=\u00a02.32, 95%CI 1.89\u20132.83); (iii) variant allele effects in two treatment subsets and valproate effects in two genotype subsets differed by 2.36\u2010fold (95%CI 1.39\u20133.67); (iv) increase in lamotrigine troughs associated with increasing valproate troughs was greater in variant allele carriers than in wild type homozygotes, i.e. variant allele effect increased with increasing valproate troughs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study is first to indicate a potentially relevant interaction between<jats:italic>ABCG2 421C&gt;A<\/jats:italic>polymorphism and valproate in their effects on lamotrigine disposition.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13646","type":"journal-article","created":{"date-parts":[[2018,5,23]],"date-time":"2018-05-23T12:49:51Z","timestamp":1527079791000},"page":"2106-2119","source":"Crossref","is-referenced-by-count":27,"title":["Interaction between<i>ABCG2 421C&gt;A<\/i>polymorphism and valproate in their effects on steady\u2010state disposition of lamotrigine in adults with epilepsy"],"prefix":"10.1111","volume":"84","author":[{"given":"Iva","family":"Klarica Domjanovi\u0107","sequence":"first","affiliation":[{"name":"Croatian Agency for Medicinal Products and Medical Devices Zagreb Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mila","family":"Lovri\u0107","sequence":"additional","affiliation":[{"name":"University Hospital Centre Zagreb Analytical Toxicology and Pharmacology Division, Department of Laboratory Diagnostics Zagreb Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir","family":"Trkulja","sequence":"additional","affiliation":[{"name":"University of Zagreb, School of Medicine Department of Pharmacology Zagreb Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u017deljka","family":"Petelin\u2010Gad\u017ee","sequence":"additional","affiliation":[{"name":"University Hospital Centre Zagreb Department of Neurology, Referral Centre for Epilepsy Zagreb Croatia"},{"name":"University of Zagreb School of Medicine Zagreb Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lana","family":"Ganoci","sequence":"additional","affiliation":[{"name":"University Hospital Centre Zagreb Division of Pharmacogenomics and Therapy Individualization, Department of Laboratory Diagnostics Zagreb Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivana","family":"\u010caji\u0107","sequence":"additional","affiliation":[{"name":"University Hospital Centre Zagreb Department of Neurology, Referral Centre for Epilepsy Zagreb Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6016-1699","authenticated-orcid":false,"given":"Nada","family":"Bo\u017eina","sequence":"additional","affiliation":[{"name":"University of Zagreb, School of Medicine Department of Pharmacology Zagreb Croatia"},{"name":"University Hospital Centre Zagreb Division of Pharmacogenomics and Therapy Individualization, Department of Laboratory Diagnostics Zagreb Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,7,8]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Medicines.org.uk Lamictal.Summary of product characteristics 2017. Available athttp:\/\/www.medicines.org.uk\/emc\/medicine\/4228(last accessed 15 August 2017)."},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01561.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-32909-3_11"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.106.009340"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-199904000-00007"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-013-0087-0"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-014-1690-1"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-014-0247-0"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2011.01.016"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-015-1925-9"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.897626"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12984"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(03)00053-5"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.113.056630"},{"key":"e_1_2_10_16_1","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1515\/dmdi-2014-0034","article-title":"Pharmacogenetics of drug metabolizing enzymes in the United Kingdom population: review of current knowledge and comparison with selected European populations","volume":"30","author":"Daly AK","year":"2015","journal-title":"Drug Metab Pers Ther"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e3283037fe4"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-017-2395-z"},{"key":"e_1_2_10_19_1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1097\/FTD.0b013e3181ceecc6","article-title":"UGT2B7_\u2010161C>T polymorphism is associated with lamotrigine concentration\u2010to\u2010dose ratio in a multivariate study","volume":"32","author":"Blanca S\u00e1nchez M","year":"2010","journal-title":"Ther Drug Monit"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-012-1449-5"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2008.08.032"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2015.01.015"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e31826517c6"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2006.00453.x"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmpk.2015.05.002"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2016.09.004"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13037"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e32835ea0b2"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1997.00594.x"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.46"},{"key":"e_1_2_10_31_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1515\/dmpt-2016-0024","article-title":"Genetic polymorphisms of cytochrome P450 enzymes: CYP2C9, CYP2C19, CYP2D6, CYP3A4 and CYP3A5 in the Croatian population","volume":"32","author":"Ganoci L","year":"2017","journal-title":"Drug Metab Pers Ther"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-8-428"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13883"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13877"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmpk.2014.12.007"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.DMPK-14-SC-041"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.09.85"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2005.11.002"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.114.058248"},{"key":"e_1_2_10_41_1","unstructured":"Fda.gov.US Food and Drug Administration: guidance for industry: drug interaction studies\u2014study design data analysis implications for dosing and labeling recommendations(2017). Available athttp:\/\/www.fda.gov\/downloads\/Drugs\/GuidanceComplianceRegulatoryInformation\/Guidances\/UCM292362.pdf(last accessed 10 November 2017)."},{"key":"e_1_2_10_42_1","unstructured":"Ema.Europa.Eu European medicines agency London UK: guideline on the investigation of drug interactions CPMP\/EWP\/560\/95\/rev. 1 Corr. 2**(2012). Available athttp:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Scientific_guideline\/2012\/07\/WC500129606.pdf(last accessed 15 August 2017)."},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1208\/aapsj070112"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3028"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2013.12"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:PHAM.0000045245.21637.d4"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-008-9752-7"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.115.066795"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.13.135"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.15.47"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djj469"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000271"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000012"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2010.01.002"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-012-1277-7"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40291-013-0041-8"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbcp.13646","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.13646","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T23:06:22Z","timestamp":1720307182000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.13646"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,8]]},"references-count":55,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2018,9]]}},"alternative-id":["10.1111\/bcp.13646"],"URL":"https:\/\/doi.org\/10.1111\/bcp.13646","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,8]]}}}