Optimising Fluvoxamine Maternal/Fetal Exposure during Gestation: A Pharmacokinetic Virtual Clinical Trials Study

Abstract

Fluvoxamine plasma concentrations have been shown to decrease throughout pregnancy. CYP2D6 polymorphisms significantly influence these changes. However, knowledge of an optimum dose adjustment according to the CYP2D6 phenotype is still limited. This study implemented a physiologically based pharmacokinetic modelling approach to assess the gestational changes in fluvoxamine maternal and umbilical cord concentrations. The optimal dosing strategies during pregnancy were simulated, and the impact of CYP2D6 phenotypes on fluvoxamine maternal and fetal concentrations was considered. A significant decrease in fluvoxamine maternal plasma concentrations was noted during gestation. As for the fetal concentration, a substantial increase was noted for the poor metabolisers (PM), with a constant level in the ultrarapid (UM) and extensive (EM) metabolisers commencing from gestation week 20 to term. The optimum dosing regimen suggested for UM and EM reached a maximum dose of 300 mg daily at gestational weeks (GW) 15 and 35, respectively. In contrast, a stable dose of 100 mg daily throughout gestation for the PM is sufficient to maintain the fluvoxamine plasma concentration within the therapeutic window (60–230 ng/mL). Dose adjustment during pregnancy is required for fluvoxamine, particularly for UM and EM, to maintain efficacy throughout the gestational period.

Publication DOI: https://doi.org/10.3390/metabo12121281
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
Aston University (General)
Additional Information: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Uncontrolled Keywords: Article,depression,pregnancy,fetal,fluvoxamine,pharmacokinetics
Publication ISSN: 2218-1989
Last Modified: 04 Nov 2024 09:13
Date Deposited: 10 Jan 2023 10:28
Full Text Link:
Related URLs: https://www.mdp ... 1989/12/12/1281 (Publisher URL)
PURE Output Type: Article
Published Date: 2022-12
Published Online Date: 2022-12-16
Accepted Date: 2022-12-11
Submitted Date: 2022-11-28
Authors: Burhanuddin, Khairulanwar
Badhan, Raj (ORCID Profile 0000-0002-0904-9324)

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