{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T02:01:21Z","timestamp":1788487281706,"version":"build-2803163510"},"reference-count":104,"publisher":"Wiley","issue":"S10","license":[{"start":{"date-parts":[[2018,9,24]],"date-time":"2018-09-24T00:00:00Z","timestamp":1537747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Safety of maternal drug therapy during breastfeeding may be assessed from estimated levels of drug exposure of the infant through milk. Pharmacokinetic (PK) principles predict that the lower the clearance is, the higher the infant dose via milk will be. Drugs with low clearance (&lt;1\u00a0mL\/[kg\u00b7min]) are likely to cause an infant exposure level greater than 10% of the weight\u2010adjusted maternal dose even if the milk\u2010to\u2010plasma concentration ratio is 1. Most drugs cause relatively low\u2010level exposure below 10% of the weight\u2010adjusted maternal dose, but opioids require caution because of their potential for severe adverse effects. Furthermore, substantial individual variations of drug clearance exist in both mother and infant, potentially causing drug accumulation over time in some infants even if an estimated dose of the drug through milk is small. Such PK differences among individuals are known not only for codeine and tramadol through pharmacogenetic variants of CYP2D6 but also for non\u2010CYP2D6 substrate opioids including oxycodone, indicating difficulties of eliminating PK uncertainty by simply replacing an opioid with another. Overall, opioid use for pain management during labor and delivery and subsequent short\u2010term use for 2\u20103 days are compatible with breastfeeding. In contrast, newly initiated and prolonged maternal opioid therapy must follow a close monitoring program of the opioid\u2010naive infants. Until more safety data become available, treatment duration of newly initiated opioids in the postpartum period should be limited to 2\u20103 days in unsupervised outpatient settings. Opioid addiction treatment with methadone and buprenorphine during pregnancy may continue into breastfeeding, but infant conditions must be monitored.<\/jats:p>","DOI":"10.1002\/jcph.1113","type":"journal-article","created":{"date-parts":[[2018,9,24]],"date-time":"2018-09-24T15:27:34Z","timestamp":1537802854000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Opioids in Breast Milk: Pharmacokinetic Principles and Clinical Implications"],"prefix":"10.1002","volume":"58","author":[{"given":"Shinya","family":"Ito","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology Hospital for Sick Children University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,24]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"OECD.Doing better for children. www.oecd.org\/els\/social\/childwellbeing. Accessed December 2 2017."},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejcn.1601799"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/bfm.2007.0010"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2011-3552"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1089\/bfm.2009.0050"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2004-2283"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-200X.2009.02877.x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2008-3256"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2006-2256"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2009.10.040"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2010-3000"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-3022"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.65.5.578"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2016.06.045"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/106002809302700110"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(95)90015-2"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.106.1.27"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200007133430208"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69255-6"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1718"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1714"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.087643"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.9.5076"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026499523505"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.377"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.111.040972"},{"issue":"8","key":"e_1_2_11_28_1","first-page":"2527","article-title":"Prediction of drug transfer into milk considering breast cancer resistance protein (BCRP)\u2010mediated transport","volume":"32","author":"Ito N","year":"2015","journal-title":"Pharm Res"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2004.10.012"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1186"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01621-06"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00323.2014"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/acps.12479"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1089\/bfm.2014.0170"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1994.tb04331.x"},{"key":"e_1_2_11_36_1","first-page":"721","article-title":"Methadone overdose in a breast\u2010feeding toddler [Abstract 95]","volume":"47","author":"West PL","year":"2009","journal-title":"Clin Toxicol (Phila)"},{"key":"e_1_2_11_37_1","first-page":"12","article-title":"Neonatal abstinence syndrome following abrupt cessation of breastfeeding","volume":"112","author":"Malpas TJ","year":"1999","journal-title":"N Z Med J"},{"key":"e_1_2_11_38_1","unstructured":"LactMed:https:\/\/toxnet.nlm.nih.gov\/newtoxnet\/lactmed.htm. Accessed January 11 2018."},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1213\/00000539-200201000-00035"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199011000-00012"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.3109\/15563659008994437"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1981.87"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1479-828X.2007.00715.x"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2008.03117.x"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1177\/0890334409333475"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03008782"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1997.t01-1-00624.x"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0306-5251.2001.01506.x"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1089\/bfm.2010.0060"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1089\/bfm.2011.0096"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-6196(11)60750-7"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200140070-00001"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aeu186"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1992.tb05652.x"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1996.03539.x"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acpain.2006.04.001"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002160"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2362.33.s2.3.x"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa041888"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200011000-00002"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2011.06.050"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1177\/089033449300900423"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.3109\/15563650.2012.681052"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2009.151"},{"key":"e_1_2_11_65_1","unstructured":"FDA Drug Safety Communication. FDA restricts use of prescription codeine pain and cough medicines and tramadol pain medicines in children; recommends against use in breastfeeding women. www.fda.gov\/Drugs\/DrugSafety\/ucm549679.htm. Accessed December 2 2017."},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2006.01.009"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-013-0036-0"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(98)90051-0"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2010.03653.x"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9592.2005.01571.x"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1991.tb03942.x"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200443130-00004"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280050368"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.CR0060032"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(96)90211-8"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aen094"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1213\/ane.0b013e31817b796e"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2014-2673"},{"key":"e_1_2_11_79_1","first-page":"336","article-title":"Fentanyl excretion in breast milk","volume":"9","author":"Leuschen MP","year":"1990","journal-title":"Clin Pharm"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1213\/00000539-198603000-00002"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2011-3212"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1999.00921.x"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1007\/s005200000180"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(88)90290-4"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2013-3524"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2005-1561"},{"key":"e_1_2_11_87_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2214.2006.00635.x"},{"key":"e_1_2_11_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/jp.2010.66"},{"key":"e_1_2_11_89_1","doi-asserted-by":"publisher","DOI":"10.1111\/apa.12378"},{"key":"e_1_2_11_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2008.08.041"},{"key":"e_1_2_11_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1701-2163(16)35245-8"},{"key":"e_1_2_11_92_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1005359"},{"key":"e_1_2_11_93_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200544070-00001"},{"key":"e_1_2_11_94_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1981.tb13848.x"},{"key":"e_1_2_11_95_1","doi-asserted-by":"publisher","DOI":"10.1177\/0890334408328295"},{"key":"e_1_2_11_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2016.03.076"},{"key":"e_1_2_11_97_1","doi-asserted-by":"publisher","DOI":"10.1177\/0890334416663198"},{"key":"e_1_2_11_98_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.2010.03170.x"},{"key":"e_1_2_11_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0376-8716(00)00194-0"},{"key":"e_1_2_11_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(97)90053-9"},{"key":"e_1_2_11_101_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1360-0443.2003.00245.x"},{"key":"e_1_2_11_102_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1360-0443.2003.00551.x"},{"key":"e_1_2_11_103_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.676"},{"key":"e_1_2_11_104_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.23"},{"key":"e_1_2_11_105_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.19"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcph.1113","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1113","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T10:19:35Z","timestamp":1694945975000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.1113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,24]]},"references-count":104,"journal-issue":{"issue":"S10","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["10.1002\/jcph.1113"],"URL":"https:\/\/doi.org\/10.1002\/jcph.1113","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,24]]},"assertion":[{"value":"2017-12-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-02-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}