The application of precision dosing in the use of sertraline throughout pregnancy for poor and ultra-rapid metaboliser CYP 2C19 subjects: a virtual clinical trial pharmacokinetics study:A virtual clinical trial pharmacokinetics study

Abstract

Sertraline is known to undergo changes in pharmacokinetics during pregnancy. CYP 2C19 has been implicated in the interindividual variation in clinical effect associated with sertraline activity. However, knowledge of suitable dose titrations during pregnancy and within CYP 2C19 phenotypes is lacking. A pharmacokinetic modeling virtual clinical trials approach was implemented to: (i) assess gestational changes in sertraline trough plasma concentrations for CYP 2C19 phenotypes, and (ii) identify appropriate dose titration strategies to stabilize sertraline levels within a defined therapeutic range throughout gestation. Sertraline trough plasma concentrations decreased throughout gestation, with maternal volume expansion and reduction in plasma albumin being identified as possible causative reasons. All CYP 2C19 phenotypes required a dose increase throughout gestation. For extensive metabolizer (EM) and ultrarapid metabolizer (UM) phenotypes, doses of 100–150 mg daily are required throughout gestation. For poor metabolizers (PM), 50 mg daily during trimester 1 followed by a dose of 100 mg daily in trimesters 2 and 3 are required.

Publication DOI: https://doi.org/10.1002/bdd.2278
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
Additional Information: © 2021 The Authors. Biopharmaceutics & Drug Disposition published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Funding Information: Certara UK (Simcyp Division) granted free access to the Simcyp Simulators through an academic license (subject to conditions). This work was supported by Kuwait University.
Uncontrolled Keywords: PBPK,pharmacokinetics,phenotype,pregnancy,sertraline,Pharmacology,Pharmaceutical Science,Pharmacology (medical)
Full Text Link:
Related URLs: https://onlinel ... 0.1002/bdd.2278 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2021-06
Published Online Date: 2021-04-13
Accepted Date: 2021-03-29
Authors: Almurjan, Aminah
MacFarlane, Hannah (ORCID Profile 0000-0002-6724-4312)
Badhan, Raj K.S. (ORCID Profile 0000-0002-0904-9324)

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