{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:22:12Z","timestamp":1783012932580,"version":"3.54.6"},"reference-count":53,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Diazepam is commonly used to treat eclampsia and anxiety associated with pregnancy\u2010induced hypertension. Although generally considered safe, diazepam undergoes extensive hepatic metabolism. Therefore, it is essential to evaluate both diazepam and its metabolites in maternal and fetal compartments to understand potential fetal exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Midgestational mice received diazepam through tail vein injection. Concentrations of diazepam and its metabolites (nordazepam, oxazepam, and oxazepam\u2010glucuronide) were quantified using liquid chromatography\u2013mass spectrometry in maternal plasma, brain, and liver, as well as in whole fetuses, fetal brains, and livers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Maternal diazepam is rapidly metabolized into oxazepam, which readily crossed the placenta. Fetal\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      values were 166.7\u00a0ng\u00b7g\n                      <jats:sup>\u22121<\/jats:sup>\n                      fetus (95% CI, 54.9\u2013278.5) for diazepam, 294.4\u00a0ng\u00b7g\n                      <jats:sup>\u22121<\/jats:sup>\n                      fetus (253.8\u2013335.0) for nordazepam, and 503.1\u00a0ng\u00b7g\n                      <jats:sup>\u22121<\/jats:sup>\n                      fetus (456.2\u2013550.0) for oxazepam, indicating higher fetal exposure to metabolites than to the parent drug. Despite its high solubility, oxazepam\u2010glucuronide, was detected in fetuses within 1\u00a0h of maternal administration and persisted at concentrations exceeding maternal plasma for up to 6\u00a0h. Relative transfer ratios (vs. maternal plasma) were &lt;1 for diazepam, nordazepam, and oxazepam but markedly higher for oxazepam\u2010glucuronide, ranging from 2.2 in the fetus to 2.9 in amniotic fluid.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Although diazepam is rapidly cleared from maternal plasma, its metabolites, particularly oxazepam\u2010glucuronide, persist and accumulate in the fetus. These findings indicate prolonged fetal exposure to these substances and suggest facilitated placental transfer of oxazepam\u2010glucuronide, with potential implications for fetal safety and maternal pharmacotherapy during pregnancy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70430","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T07:41:28Z","timestamp":1777275688000},"page":"4288-4304","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Liquid chromatography\u2013mass spectrometry\u2010based characterization of maternal\u2013fetal pharmacokinetics of diazepam and its metabolites in pregnant mice"],"prefix":"10.1111","volume":"183","author":[{"given":"Yuta","family":"Takahashi","sequence":"first","affiliation":[{"name":"Department of Pharmacokinetics, School of Pharmacy and Pharmaceutical Sciences Hoshi University  Tokyo 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