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Spinal, epidural and intravenous fentanyl has been studied in pregnant women and neonates, but foetal safety of fentanyl dosing with transdermal patch during pregnancy and labour is not sufficiently studied. Foetal <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content> is physiologically lower than maternal <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content>, and thus, opioids, which are weak bases, are ionized and may cumulate to foetus. Foetal asphyxia may further worsen acidosis, and ion trapping induced by low <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content> is assumed to increase the foetal exposure to opioids. Here, we show that no correlation between foetal acidosis and ion trapping of fentanyl could be found. In three experiments, 29 pregnant sheep were administered fentanyl with 2 \u03bcg\/kg\/h patch supplemented with <jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content> boluses\/infusion. Foetal exposure to fentanyl was extensive, median 0.34 ng\/ml (quartiles 0.21, 0.42), yet drug accumulation to foetus was not observed, and median of foetal\/maternal concentration (F\/M) ratio was 0.63 (0.43, 0.75) during the first hours after the fentanyl administration. Low foetal <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content> difference between ewe and the foetus did not correlate with fentanyl concentration in the foetus or F\/M ratio. At steady\u2010state during the second patch worn, foetal plasma fentanyl was low, 0.13 ng\/ml, and the median of F\/M ratio was 0.69. Our results demonstrate that drug accumulation to foetus caused by ion trapping seen with some weak base opioids may not be that significant with fentanyl. These results have a clinical relevance when fentanyl is dosed to pregnant woman and the foetus is acidemic.<\/jats:p>","DOI":"10.1111\/bcpt.12665","type":"journal-article","created":{"date-parts":[[2016,9,8]],"date-time":"2016-09-08T14:27:32Z","timestamp":1473344852000},"page":"195-198","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Foetal Fentanyl Exposure and Ion Trapping after Intravenous and Transdermal Administration to the Ewe"],"prefix":"10.1111","volume":"120","author":[{"given":"Emma M.","family":"Heikkinen","sequence":"first","affiliation":[{"name":"School of Pharmacy University of Eastern Finland Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannu","family":"Kokki","sequence":"additional","affiliation":[{"name":"Anaesthesia and Operative Services Kuopio University Hospital Kuopio Finland"},{"name":"School of Medicine University of Eastern Finland Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aki","family":"Heikkinen","sequence":"additional","affiliation":[{"name":"Admescope Ltd Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veli\u2010Pekka","family":"Ranta","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Eastern Finland Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha","family":"R\u00e4s\u00e4nen","sequence":"additional","affiliation":[{"name":"School of Medicine University of Eastern Finland Kuopio Finland"},{"name":"Department of Obstetrics and Gynaecology Kuopio University Hospital Kuopio Finland"},{"name":"Department of Obstetrics and Gynaecology Oulu University Hospital Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna\u2010Marja","family":"Voipio","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre Department of Experimental Surgery University 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