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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: CLINICAL PHARMACOLOGY & THERAPEUTICS; v. 105, n. 4, p. 1003-1008, APR 2019.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 13/00346-4 - Pharmacokinetics and analysis of transplacental distribution of fluoxetine and its metabolite in pregnant women with gestational Diabetes mellitus
• Grantee: Elaine Christine Dantas Moisés
• Support Opportunities: Regular Research Grants