{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:00:39Z","timestamp":1788454839827,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T00:00:00Z","timestamp":1667520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673510"],"award-info":[{"award-number":["81673510"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073936"],"award-info":[{"award-number":["82073936"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The pharmacokinetics of levetiracetam (LEV) significantly changed during pregnancy. It is a great challenge to predict the adjusted doses of LEV to reach the preconception target concentrations. This study aimed to establish a population pharmacokinetic model of LEV in women with epilepsy (WWE) during pregnancy to analyse the factors of pharmacokinetic variability and to develop a model\u2010based individualized dosing regimen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 166 concentration\u2013time points from 37 WWE during pregnancy treated with LEV were collected to analyse LEV pharmacokinetics with nonlinear mixed\u2010effects modelling. The dosing regimen was optimized by Monte Carlo simulations based on the final model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The LEV pharmacokinetics in pregnant WWE were best described by a 1\u2010compartment model of first\u2010order absorption and elimination. The population typical value of apparent clearance (CL\/F) in the final model was estimated to be 3.82\u2009L\/h (95% confidence interval 3.283\u20134.357\u2009L\/h) with a relative standard error of 7.2%. Both total body weight (TBW) and trimester of pregnancy were significantly associated with LEV\u2010CL\/F during pregnancy; LEV\u2010CL\/F increased by 42.72% when TBW increased from 55 to 65\u2009kg from the first trimester to the second trimester. Monte Carlo simulations showed that dosing regimens for LEV should be individualized based on the patient's TBW and trimester of pregnancy to maximize the likelihood of achieving the therapeutic range.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This first population pharmacokinetic study of LEV in WWE during pregnancy supports the use of a weight\u2010based and pregnancy\u2010based dosing regimen and can lay a foundation for further optimizing the individualized dosing regimens.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15572","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T15:24:17Z","timestamp":1666193057000},"page":"1152-1161","source":"Crossref","is-referenced-by-count":13,"title":["Population pharmacokinetics and dosing regimen optimization of levetiracetam in epilepsy during pregnancy"],"prefix":"10.1111","volume":"89","author":[{"given":"Ying","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacy Shengjing Hospital of China Medical University  Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming\u2010Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shengjing Hospital of China Medical University  Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurology Shengjing Hospital of China Medical University  Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun\u2010Feng","family":"Cao","sequence":"additional","affiliation":[{"name":"Shanghai Institute for Biomedical and Pharmaceutical Technologies, NHC Key Laboratory of Reproduction Regulation  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4566-9608","authenticated-orcid":false,"given":"Ming\u2010Ming","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shengjing Hospital of China Medical University  Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8573-8028","authenticated-orcid":false,"given":"Li\u2010Mei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shengjing Hospital of China Medical University  Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.307.6902.492"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0733\u20108619(18)30075\u20106"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010020\u201009764\u2010w"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2004.07.004"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(12)70103\u20105"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2008.04.022"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(12)70323\u2010X"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.15968"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.2165\/11317640\u2010000000000\u201000000"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.00330"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2016.11.018"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.0447"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(18)30107\u20108"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182088297"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000030"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2013.06.026"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000158"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000291"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2017.02.011"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2020.02.018"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.DMPK\u201013\u2010RG\u2010045"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088\u2010200847050\u201000004"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2020.1746981"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13709"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.1994.tb05705.x"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105610"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003\u20104819\u2010145\u20104\u2010200608150\u201000004"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006240"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12109"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20103252\u20108_4"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2010.12.018"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.532"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088\u2010200746060\u201000004"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.14"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.2165\/11318080\u2010000000000\u201000000"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.26"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.29"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088\u2010200443110\u201000002"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0950\u20103552(05)80319\u20100"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088\u2010199835010\u201000004"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163\u20107258(99)00052\u20102"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e31825ee389"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2011.01.007"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2010.05.008"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528\u20101167.2008.01561.x"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181a6b312"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.15572","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcp.15572","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.15572","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T11:37:17Z","timestamp":1692272237000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.15572"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,4]]},"references-count":47,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1111\/bcp.15572"],"URL":"https:\/\/doi.org\/10.1111\/bcp.15572","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,4]]}}}