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Benzodiazepine Concentrations in the Breast milk and Plasma of Nursing Mothers : Estimation of Relative Infant Dose

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Title: Benzodiazepine Concentrations in the Breast milk and Plasma of Nursing Mothers : Estimation of Relative Infant Dose
Authors: Nishimura, Ayako Browse this author
Furugen, Ayako Browse this author →KAKEN DB
Umazume, Takeshi Browse this author
Kitamura, Seika Browse this author
Soma, Mayuko Browse this author
Noshiro, Kiwamu Browse this author
Takekuma, Yoh Browse this author →KAKEN DB
Sugawara, Mitsuru Browse this author →KAKEN DB
Iseki, Ken Browse this author →KAKEN DB
Kobayashi, Masaki Browse this author →KAKEN DB
Keywords: benzodiazepines
breast milk
relative infant dose
plasma ratio
Issue Date: 15-Jan-2021
Publisher: Mary Ann Liebert
Journal Title: Breastfeeding Medicine
Publisher DOI: 10.1089/bfm.2020.0259
PMID: 33449825
Abstract: Objective: Benzodiazepines are common therapies for mental illness and insomnia, and are used during pregnancy and lactation. Although benzodiazepines have been shown to be transferred into breast milk, the amount transferred is small and compatible with breastfeeding. However, information is not available for all drugs. Therefore, we aimed to determine the milk to plasma (M/P) ratio and relative infant dose (RID), which are used as indicators of drug transfer to breast milk, to determine the safety of such drugs for lactating women and breastfeeding infants. Methods: The study comprised of 11 pregnant women who visited the obstetrics department of Hokkaido University Hospital (approval number: 017-0131) and Tenshi Hospital (approval number: 103) for childbirth. The samples were analyzed using liquid chromatography-tandem mass spectrometry, and the M/P ratio and RID were calculated. The condition of the mother and baby at 1 month after delivery was determined from the clinical information. The target benzodiazepines were alprazolam, brotizolam, clonazepam, clotiazepam, etizolam, ethyl loflazepate, flunitrazepam, and lorazepam. Results: For all drugs, the M/P ratios were <1 and remained constant over time. For drugs other than ethyl loflazepate, the RID values were <10%, which are considered safe; however, even with ethyl loflazepate, it was only slightly >10%. No abnormalities were found in breastfeeding infants whose mothers were receiving these medications. Conclusions: The RID results of this study suggest that drug exposure through breast milk is small; thus, maternal drug treatment and breastfeeding are compatible.
Rights: This is the accepted version of the following article: Ayako Nishimura et al. Benzodiazepine Concentrations in the Breast milk and Plasma of Nursing Mothers: Estimation of Relative Infant Dose, Breastfeed Med. 2021, which has now been formally published in final form at Breastfeeding Medicine at 10.1089/bfm.2020.0259. This original submission version of the article may be used for non-commercial purposes in accordance with the Mary Ann Liebert, Inc., publishers’ self-archiving terms and conditions.
Type: article (author version)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 古堅 彩子

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