alexa Metabolism And Transplacental Distribution Of Metoprolol And Its Metabolites Isomers In Parturients With Well-controlled Gestational Diabetes Mellitus | 19804
ISSN: 0975-0851

Journal of Bioequivalence & Bioavailability
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Natal?cia de Jesus Antunes, Ricardo Carvalho Cavalli, Maria Paula Marques, Elaine Christine Dantas Moises and Vera Lucia Lanchote
Posters: J Bioequiv Availab
DOI: 10.4172/0975-0851.S1.018
Abstract
M etoprolol is a drug indicated in the treatment of hypertension during pregnancy. This study aimed to investigate the influence of gestational diabetes mellitus (GDM) on the kinetic disposition and transplacental and amniotic fluid distribution of the isomers of metoprolol, α -hydroxymetoprolol and O-desmethylmetoproloic acid in hypertensive parturients. The study was conducted on hypertensive parturients with well-controlled GDM (n=11) and non-diabetic hypertensive parturients (n=24) with a gestational age of 35 to 42 weeks, all receiving a single 100 mg oral dose of racemic metoprolol tartrate. Serial maternal blood samples (0-24 h) and umbilical blood and amniotic fluid samples were collected for the quantitation of metoprolol and its metabolites isomers using LC-MS/MS or fluorescence detection. The kinetic disposition of metoprolol and its metabolites was stereoselective in diabetic and control groups. Well-controlled GDM prolonged t max for both isomers of metoprolol (1.5 vs 2.5 h - R-(+)-MET; 1.5 vs 2.75 h - S-(-)-MET), of O-desmethylmetoproloic acid (2.0 vs 3.5 h- R-(+)- OAMD; 2.0 vs 3.0 h- S-(-)-OAMD), and of α -hydroxymetoprolol (2.0 vs 3.0 h for isomers 1'S,2R-; 1'R,2R- and 1'R,2S-OHM; 2.0 vs. 3.5 h or isomer 1'S,2S-OHM) and reduced the transplacental distribution of isomers 1?S,2S; 1?R,2R; and 1?R,2S-OHM by approximately 20%. The kinetic disposition of metoprolol was stereoselective, with plasma accumulation of the S-(-)-MET eutomer. Well-controlled GDM prolonged the tmax of metoprolol and its metabolites isomers and reduced by about 20% the transplacental distribution of the 1?S,2S, 1?R,2R, and 1?R,2S-OHM isomers. Thus, well-controlled GDM did not change the activity of CYP2D6 and CYP3A involved in metoprolol metabolism
Biography
Natal?cia de Jesus Antunes has completed her Master degree at age 27 years from School of Pharmaceutical Sciences of Ribeir?o Preto, University of S?o Paulo. She is PhD student at the School of Pharmaceutical Sciences of Ribeir?o Preto, University of S?o Paulo. She did a PhD internship at the Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University. She has worked with PK/PD modelling and pharmacokinetics studies of antihypertensive drugs during the pregnancy
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