{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:32:25Z","timestamp":1786977145024,"version":"build-2736575974"},"reference-count":65,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:00:00Z","timestamp":1667347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Many mothers need to take some medications during breastfeeding, which may carry a risk to breastfed infants. Thus, determining the amount of a drug transferred into breast milk is critical for risk\u2013benefit analysis of breastfeeding. Breast cancer resistance protein (BCRP), an efflux transporter which usually protects the body from environmental and dietary toxins, was reported to be highly expressed in lactating mammary glands. In this study, we developed a mechanistic lactation physiologically based pharmacokinetic (PBPK) modeling approach incorporating BCRP mediated transport kinetics to simulate the concentration\u2013time profiles of five BCRP drug substrates (acyclovir, bupropion, cimetidine, ciprofloxacin, and nitrofurantoin) in nursing women\u2019s plasma and milk. Due to the lack of certain physiological parameters and scaling factors in nursing women, we combine the bottom up and top down PBPK modeling approaches together with literature reported data to optimize and determine a set of parameters that are applicable for all five drugs. The predictive performance of the PBPK models was assessed by comparing predicted pharmacokinetic profiles and the milk\u2010to\u2010plasma (M\/P) ratio with clinically reported data. The predicted M\/P ratios for acyclovir, bupropion, cimetidine, ciprofloxacin, and nitrofurantoin were 2.48, 3.70, 3.55, 1.21, and 5.78, which were all within 1.5\u2010fold of the observed values. These PBPK models are useful to predict the PK profiles of those five drugs in the milk for different dosing regimens. Furthermore, the approach proposed in this study will be applicable to predict pharmacokinetics of other transporter substrates in the milk.<\/jats:p>","DOI":"10.1002\/bdd.2335","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T15:18:48Z","timestamp":1666279128000},"page":"221-232","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Physiologically based pharmacokinetic model to predict drug concentrations of breast cancer resistance protein substrates in milk"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9268-8230","authenticated-orcid":false,"given":"Tao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences SUNY\u2010Binghamton University  Johnson City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0416-2731","authenticated-orcid":false,"given":"Peng","family":"Zou","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo, Inc  Basking Ridge New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingsi","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences SUNY\u2010Binghamton University  Johnson City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Li","sequence":"additional","affiliation":[{"name":"School of Food and Agriculture College of Natural Sciences, Forestry, and Agriculture University of Maine  Orono Maine USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12662"},{"issue":"8","key":"e_1_2_10_3_1","first-page":"594","article-title":"Drug use during breast\u2010feeding","volume":"10","author":"Anderson P. O.","year":"1991","journal-title":"Clinical Pharmacology"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.377"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.1988.tb03334.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088\u2010199018020\u201000005"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0163\u20107258(93)90072\u2010l"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0190\u20109622(95)91362\u20109"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/106002809302700406"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.29252\/wjps.10.1.108"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000401065"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600581114"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010018\u20100657\u20102"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0890334418775630"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2016.03.015"},{"key":"e_1_2_10_16_1","volume-title":"Clinical lactation studies: Considerations for study design guidance for industry","author":"FDA","year":"2019"},{"key":"e_1_2_10_17_1","volume-title":"Pregnancy, lactation, and reproductive potential: Labeling for human prescription drug and biological products \u2014 content and format guidance for industry","author":"FDA","year":"2020"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0169\u2010409x(03)00032\u20102"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600760302"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx313"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11102372"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.21.7.669.34574"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002\u20109343(89)90021\u20101"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1875\u20109114.1983.tb03274.x"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0022\u20103468(05)80106\u2010x"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.111.038323"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2012.07.020"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2010.06.025"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.112.197046"},{"issue":"7","key":"e_1_2_10_30_1","first-page":"471","article-title":"Carrier\u2010mediated placental transport of cimetidine and valproic acid across differentiating JEG\u20103 cell layers","volume":"70","author":"Ikeda K.","year":"2015","journal-title":"Pharmazie"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095\u2010013\u20101085\u20105"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(03)13811\u20101"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1186"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/inf.0b013e3181fe353d"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2004.12.015"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.119.088674"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.180398"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.111.040972"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2010.08.005"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1c379"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1875\u20109114.1988.tb04058.x"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvp.12045"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.290.6481.1588\u2010a"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.105.008219"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.104.010439"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.12688\/aasopenres.12860.1"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009\u20109236(95)90175\u20102"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095\u2010015\u20101773\u20104"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469\u20107580.2005.00417.x"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095\u2010006\u20109210\u20103"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1080\/03639040701655952"},{"key":"e_1_2_10_52_1","unstructured":"Simcyp. (2021).Transporter focused workshop."},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.22080"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088\u2010198308060\u201000001"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.4088\/pcc.v06n0403"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1020483911355"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1693"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2017.10.008"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.3390\/ani11030714"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.0800047"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.676"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.m113.037309"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2011.10.004"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0151904"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfr141"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095\u2010005\u20108716\u20104"}],"container-title":["Biopharmaceutics &amp; Drug Disposition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdd.2335","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bdd.2335","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdd.2335","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T03:52:33Z","timestamp":1692503553000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdd.2335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,2]]},"references-count":65,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1002\/bdd.2335"],"URL":"https:\/\/doi.org\/10.1002\/bdd.2335","archive":["Portico"],"relation":{},"ISSN":["0142-2782","1099-081X"],"issn-type":[{"value":"0142-2782","type":"print"},{"value":"1099-081X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,2]]},"assertion":[{"value":"2022-06-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}