{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:04:10Z","timestamp":1791227050784,"version":"4.1.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The pharmacokinetics of lamotrigine (LTG) is complex and varies significantly among individuals, especially among children. Therefore, this study aimed to establish a population pharmacokinetic (PPK) model of LTG in Chinese children with epilepsy and to comprehensively evaluate the effects of genetic variations in drug-metabolizing enzymes, transporters, and a transcriptional regulator on LTG pharmacokinetics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Three hundred eighty-five steady-state plasma concentrations were obtained from 179 children (age 10.72 \u00b1 3.05 years and body weight 46.23 \u00b1 17.77 kg) with epilepsy during therapeutic drug monitoring. These patients were divided into the PPK-model group (n = 121) and the PPK-validation group (n = 58) and were genotyped for\n                      <jats:italic toggle=\"yes\">UGT1A4<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">UGT2B7<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">ABCB1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">ABCG2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">SLC22A1<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">HNF4\u03b1<\/jats:italic>\n                      . PPK analysis was performed by nonlinear mixed effects modeling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      In the final model, apparent clearance (CL\/F) of LTG was estimated to be 1.48 L\/h; 500 mg valproic acid, oxcarbazepine, and\n                      <jats:italic toggle=\"yes\">UGT2B7<\/jats:italic>\n                      -161TT genotype changed the CL\/F by \u221246.2, +31.1, and \u221221.8%, respectively. Body weight was also identified as a significant covariate affecting LTG CL\/F.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      A PPK\u2013pharmacogenetic model of LTG in Chinese children with epilepsy was successfully established with nonlinear mixed effects modeling. Genotyping for\n                      <jats:italic toggle=\"yes\">UGT2B7<\/jats:italic>\n                      -161C&gt;T may be useful in titrating the optimal LTG dose.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1097\/ftd.0000000000000563","type":"journal-article","created":{"date-parts":[[2018,8,31]],"date-time":"2018-08-31T03:15:35Z","timestamp":1535685335000},"page":"730-737","source":"Crossref","is-referenced-by-count":16,"title":["A Population Pharmacokinetic\u2013Pharmacogenetic Model of Lamotrigine in Chinese Children With Epilepsy"],"prefix":"10.1097","volume":"40","author":[{"given":"Yanan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Shengjing Hospital of China Medical University;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shansen","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shengjing Hospital of China Medical 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