Carvalho Daniela Miarelli, Nardotto Glauco Henrique Balthazar, Filgueira Gabriela Campos de Oliveira, Duarte Geraldo, Cavalli Ricardo Carvalho, Lanchote Vera Lucia, Moisés Elaine Christine Dantas
Department of Obstetrics and Gynecology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil.
Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-903, SP, Brazil.
Pharmaceutics. 2024 Dec 30;17(1):35. doi: 10.3390/pharmaceutics17010035.
: 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). : 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. : The area under the plasma over time curve (AUC) 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. : 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.
氟西汀（FLX）是治疗抑郁症的孕妇中最常开具的5-羟色胺再摄取抑制剂。本研究评估了妊娠期糖尿病（GDM）对FLX及其代谢产物去甲氟西汀（norFLX）的对映体选择性药代动力学和经胎盘分布的影响。：10名被诊断为GDM的孕妇（GDM组）在妊娠晚期血糖控制良好后接受研究。她们单次口服20mg FLX，并在0至672小时采集血样。分娩当天，在再次单次口服20mg FLX后，在出生时采集母血、脐血和绒毛间隙血样。使用Kruskal-Wallis秩和检验及Dunn-Bonferroni事后检验，将诊断为GDM的孕妇获得的药代动力学参数与一组先前研究的健康孕妇（n = 9）进行比较。：FLX的R-(+)-和S-(-)-对映体的血浆药时曲线下面积（AUC）分别为197.93和109.62 ng∙h/mL，norFLX的分别为600.39和960.83 ng∙h/mL。FLX和norFLX对映体的脐静脉/母血静脉比率接近0.3，表明胎盘转运较低。FLX和norFLX对映体的脐动脉/脐静脉比率均接近0.7，表明胎儿代谢不存在或很少。：GDM并未改变妊娠晚期血糖控制良好的患者中FLX和norFLX对映体的药代动力学。
