Trial reportBritish journal of clinical pharmacology2015
Influence of gestational diabetes on the stereoselective pharmacokinetics and placental distribution of metoprolol and its metabolites in parturients.
Trial report in British journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 17 citations in OpenAlex.
- Enantioselective transplacental transfer of xenobiotics: mechanisms, plasma protein binding, and health implications for fetal development.Archives of toxicology · 2025Review
- Gestational Diabetes Mellitus Does Not Change the Pharmacokinetics and Transplacental Distribution of Fluoxetine and Norfluoxetine Enantiomers.Pharmaceutics · 2024Article
- Review
- Utilizing Amniotic Fluid Metabolomics to Monitor Fetal Well-Being: A Narrative Review of the Literature.Cureus · 2023Review
- Prediction of maternal pharmacokinetics using physiologically based pharmacokinetic models: assessing the impact of the longitudinal changes in the activity of CYP1A2, CYP2D6 and CYP3A4 enzymes during pregnancy.Journal of pharmacokinetics and pharmacodynamics · 2020Article
- Imbalance of Drug Transporter-CYP450s Interplay by Diabetes and Its Clinical Significance.Pharmaceutics · 2020Review
- Effect of Naoxintong Capsules on the Activities of CYP450 and Metabolism of Metoprolol Tartrate in Rats Evaluated by Probe Cocktail and Pharmacokinetic Methods.Evidence-based complementary and alternative medicine : eCAM · 2019Article
- A method to determine pharmacokinetic parameters based on andante constant-rate intravenous infusion.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo investigate the influence of gestational diabetes mellitus (GDM) on the kinetic disposition and transplacental and amniotic fluid distribution of metoprolol and its metabolites O-desmethylmetoproloic acid and α-hydroxymetoprolol stereoisomers in hypertensive parturients receiving a single dose of the racemic drug.
methodsThe study was conducted on hypertensive parturients with well-controlled GDM (n = 11) and non-diabetic hypertensive parturients (n = 24), all receiving a single 100 mg oral dose of racemic metoprolol tartrate before delivery. Serial maternal blood samples (0-24 h) and umbilical blood and amniotic fluid samples were collected for the quantitation of metoprolol and its metabolite stereoisomers using LC-MS/MS or fluorescence detection.
resultsThe kinetic disposition of metoprolol and its metabolites was stereoselective in the diabetic and control groups. Well-controlled GDM prolonged tmax for both enantiomers of metoprolol (1.5 vs. 2.5 h R-(+)-MET; 1.5 vs. 2.75 h S-(-)-MET) and O-desmethylmetoproloic acid (2.0 vs. 3.5 h R-(+)-AOMD; 2.0 vs. 3.0 h S-(-)-OAMD), and for the four stereoisomers of α-hydroxymetoprolol (2.0 vs. 3.0 h for 1'S,2R-, 1'R,2R- and 1'R,2S-OHM; 2.0 vs. 3.5 h for 1'S,2S-OHM) and reduced the transplacental distribution of 1'S,2S-, 1'R,2R-, and 1'R,2S-OHM by approximately 20%.
conclusionsThe kinetic disposition of metoprolol was enantioselective, with plasma accumulation of the S-(-)-MET eutomer. Well-controlled GDM prolonged the tmax of metoprolol and O-desmethylmetoproloic acid enantiomers and the α-hydroxymetoprolol stereoisomers and reduced by about 20% the transplacental distribution of 1'S,2S-, 1'R,2R-, and 1'R,2S-OHM. Thus, well-controlled GDM did not change the activity of CYP2D6 and CYP3A involved in metoprolol metabolism.
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