Pharmacokinetics and Transplacental Transfer of Fluoxetine Enantiomers and Their Metabolites in Pregnant Women

Autor(es)

Carvalho, Daniela Miarelli ^[1] ; Lanchote, Vera Lucia ^[2] ; de Oliveira Filgueira, Gabriela Campos ^[1] ; Balthazar Nardotto, Glauco Henrique ^[2] ; Duarte, Geraldo ^[1] ; Cavalli, Ricardo Carvalho ^[1] ; Dantas Moises, Elaine Christine ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Obstet & Gynecol, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Toxicol & Bromatol Anal, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CLINICAL PHARMACOLOGY & THERAPEUTICS; v. 105, n. 4, p. 1003-1008, APR 2019.
• Citações Web of Science: 0

Resumo

Considering that fluoxetine (FLX) is used to treat depressive states during pregnancy and that it is a cytochrome P450 (CYP)2D6 inhibitor, which is involved in the metabolism of both of its enantiomers, this study aims to describe the enantioselective distribution and metabolism of FLX and of its metabolite norfluoxetine (NorFLX) following a single oral dose. Nine healthy pregnant women received 20 mg FLX at 32 weeks of gestation and later at the day of delivery. The apparent clearance of (S)-(+)-FLX (1.45 vs. 0.66 L/hour/kg) and the area under the plasma concentration vs. time curve (AUC) of the (S)-(+)-NorFLX (AUC(0-infinity) 942.7 vs. 498.6 ng hour/mL) were higher (P < 0.05) than those of the respective (R)-(-) enantiomers, indicating that the (S)-(+)-FLX enantiomer is preferentially metabolized to (S)-(+)-NorFLX. The placental transfer (umbilical vein/maternal vein) of FLX and NorFLX is low (30-40%), with the predominant transfer of (S)-(+)-FLX (44 vs. 33%). The distribution of the enantiomers of FLX and NorFLX to amniotic fluid is low (< 10%). (AU)

• Processo FAPESP: 13/00346-4 - Estudo farmacocinético e análise da distribuição transplacentária da fluoxetina e seu metabólito em gestantes portadoras de Diabetes mellitus gestacional
• Beneficiário: Elaine Christine Dantas Moisés
• Modalidade de apoio: Auxílio à Pesquisa - Regular