Gestational Diabetes Mellitus Does Not Change the Pharmacokinetics and Transplacental Distribution of Fluoxetine and Norfluoxetine Enantiomers

<b>Background/Objectives</b>: Fluoxetine (FLX) is the inhibitor of serotonin reuptake most prescribed in pregnant women with depression. This study evaluates the influence of gestational diabetes mellitus (GDM) on the enantioselective pharmacokinetics and transplacental distribution of F...

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Main Authors: Daniela Miarelli Carvalho, Glauco Henrique Balthazar Nardotto, Gabriela Campos de Oliveira Filgueira, Geraldo Duarte, Ricardo Carvalho Cavalli, Vera Lucia Lanchote, Elaine Christine Dantas Moisés
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Language:English
Published: MDPI AG 2024-12-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/1/35
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author Daniela Miarelli Carvalho
Glauco Henrique Balthazar Nardotto
Gabriela Campos de Oliveira Filgueira
Geraldo Duarte
Ricardo Carvalho Cavalli
Vera Lucia Lanchote
Elaine Christine Dantas Moisés
author_facet Daniela Miarelli Carvalho
Glauco Henrique Balthazar Nardotto
Gabriela Campos de Oliveira Filgueira
Geraldo Duarte
Ricardo Carvalho Cavalli
Vera Lucia Lanchote
Elaine Christine Dantas Moisés
author_sort Daniela Miarelli Carvalho
collection DOAJ
description <b>Background/Objectives</b>: Fluoxetine (FLX) is the inhibitor of serotonin reuptake most prescribed in pregnant women with depression. This study evaluates the influence of gestational diabetes mellitus (GDM) on the enantioselective pharmacokinetics and transplacental distribution of FLX and its metabolite norfluoxetine (norFLX). <b>Methods</b>: Ten pregnant women diagnosed with GDM (GDM group) were investigated in the third trimester of gestation after they achieved good glycemic control. They received a single oral dose of 20 mg FLX, and blood samples were collected from 0 to 672 h. On the day of delivery, after another single oral dose of 20 mg FLX, blood samples of maternal vein, umbilical vessels and intervillous space were collected at birth. The pharmacokinetics parameters obtained for pregnant women diagnosed with GDM were compared with a group of healthy pregnant women (n = 9) previously investigated using Kruskal–Wallis’s rank-sum test with the Dunn–Bonferroni post hoc test. <b>Results</b>: The area under the plasma over time curve (AUC<sub>0–∞</sub>) were 197.93 and 109.62 ng∙h/mL for FLX and 600.39 and 960.83 ng∙h/mL for norFLX, respectively, for their R-(+)- and S-(-)- enantiomers. The umbilical vein/maternal vein ratio for FLX and norFLX enantiomers was nearly 0.3, inferring low placental transfer. The umbilical artery/umbilical vein ratios were nearly 0.7 for both FLX and norFLX enantiomers, indicating absence or small fetal metabolism. <b>Conclusions</b>: The GDM did not alter the pharmacokinetics of FLX and norFLX enantiomers in patients with good glycemic control evaluated in the third trimester of gestation.
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spelling doaj-art-440430ceece249b694d48a55e38aaafc2025-01-24T13:45:39ZengMDPI AGPharmaceutics1999-49232024-12-011713510.3390/pharmaceutics17010035Gestational Diabetes Mellitus Does Not Change the Pharmacokinetics and Transplacental Distribution of Fluoxetine and Norfluoxetine EnantiomersDaniela Miarelli Carvalho0Glauco Henrique Balthazar Nardotto1Gabriela Campos de Oliveira Filgueira2Geraldo Duarte3Ricardo Carvalho Cavalli4Vera Lucia Lanchote5Elaine Christine Dantas Moisés6Department of Obstetrics and Gynecology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, BrazilDepartment of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-903, SP, BrazilDepartment of Obstetrics and Gynecology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, BrazilDepartment of Obstetrics and Gynecology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, BrazilDepartment of Obstetrics and Gynecology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, BrazilDepartment of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-903, SP, BrazilDepartment of Obstetrics and Gynecology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil<b>Background/Objectives</b>: Fluoxetine (FLX) is the inhibitor of serotonin reuptake most prescribed in pregnant women with depression. This study evaluates the influence of gestational diabetes mellitus (GDM) on the enantioselective pharmacokinetics and transplacental distribution of FLX and its metabolite norfluoxetine (norFLX). <b>Methods</b>: Ten pregnant women diagnosed with GDM (GDM group) were investigated in the third trimester of gestation after they achieved good glycemic control. They received a single oral dose of 20 mg FLX, and blood samples were collected from 0 to 672 h. On the day of delivery, after another single oral dose of 20 mg FLX, blood samples of maternal vein, umbilical vessels and intervillous space were collected at birth. The pharmacokinetics parameters obtained for pregnant women diagnosed with GDM were compared with a group of healthy pregnant women (n = 9) previously investigated using Kruskal–Wallis’s rank-sum test with the Dunn–Bonferroni post hoc test. <b>Results</b>: The area under the plasma over time curve (AUC<sub>0–∞</sub>) were 197.93 and 109.62 ng∙h/mL for FLX and 600.39 and 960.83 ng∙h/mL for norFLX, respectively, for their R-(+)- and S-(-)- enantiomers. The umbilical vein/maternal vein ratio for FLX and norFLX enantiomers was nearly 0.3, inferring low placental transfer. The umbilical artery/umbilical vein ratios were nearly 0.7 for both FLX and norFLX enantiomers, indicating absence or small fetal metabolism. <b>Conclusions</b>: The GDM did not alter the pharmacokinetics of FLX and norFLX enantiomers in patients with good glycemic control evaluated in the third trimester of gestation.https://www.mdpi.com/1999-4923/17/1/35fluoxetinenorfluoxetineenantiomerspharmacokineticspregnancyplacental transfer
spellingShingle Daniela Miarelli Carvalho
Glauco Henrique Balthazar Nardotto
Gabriela Campos de Oliveira Filgueira
Geraldo Duarte
Ricardo Carvalho Cavalli
Vera Lucia Lanchote
Elaine Christine Dantas Moisés
Gestational Diabetes Mellitus Does Not Change the Pharmacokinetics and Transplacental Distribution of Fluoxetine and Norfluoxetine Enantiomers
Pharmaceutics
fluoxetine
norfluoxetine
enantiomers
pharmacokinetics
pregnancy
placental transfer
title Gestational Diabetes Mellitus Does Not Change the Pharmacokinetics and Transplacental Distribution of Fluoxetine and Norfluoxetine Enantiomers
title_full Gestational Diabetes Mellitus Does Not Change the Pharmacokinetics and Transplacental Distribution of Fluoxetine and Norfluoxetine Enantiomers
title_fullStr Gestational Diabetes Mellitus Does Not Change the Pharmacokinetics and Transplacental Distribution of Fluoxetine and Norfluoxetine Enantiomers
title_full_unstemmed Gestational Diabetes Mellitus Does Not Change the Pharmacokinetics and Transplacental Distribution of Fluoxetine and Norfluoxetine Enantiomers
title_short Gestational Diabetes Mellitus Does Not Change the Pharmacokinetics and Transplacental Distribution of Fluoxetine and Norfluoxetine Enantiomers
title_sort gestational diabetes mellitus does not change the pharmacokinetics and transplacental distribution of fluoxetine and norfluoxetine enantiomers
topic fluoxetine
norfluoxetine
enantiomers
pharmacokinetics
pregnancy
placental transfer
url https://www.mdpi.com/1999-4923/17/1/35
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