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Population pharmacokinetics of esomeprazole in patients with preterm preeclampsia
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  • Manna Semere Gebreyesus,
  • Eric Decloedt,
  • Catherine A Cluver,
  • Nicole Hunfeld,
  • Holmfridur Helgadottir,
  • Einar Björnsson,
  • Roeland Wasmann,
  • Paolo Denti
Manna Semere Gebreyesus
University of Cape Town Faculty of Health Sciences

Corresponding Author:smrman003@myuct.ac.za

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Eric Decloedt
Stellenbosch University - Tygerberg Campus
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Catherine A Cluver
Stellenbosch University - Tygerberg Campus
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Nicole Hunfeld
Erasmus University Rotterdam
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Holmfridur Helgadottir
Landspitali haskolasjukrahus
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Einar Björnsson
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Roeland Wasmann
University of Cape Town Faculty of Health Sciences
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Paolo Denti
University of Cape Town Faculty of Health Sciences
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Abstract

Esomeprazole is a proton pump inhibitor being investigated for treatment of preeclampsia. Esomeprazole pharmacokinetics during pregnancy is unknown. We used data from 10 pregnant patients with preterm preeclampsia, and 49 non-pregnant individuals to develop a population pharmacokinetic model of esomeprazole. A two-compartment model described the data well. In pregnant patients after single dose, clearance was 42.2% (14.9%– 61.6%) lower compared to non-pregnant, most likely due to downregulation of CYP2C19. In non-pregnant after repeated dosing, clearance was 54.9% (48.2% – 63.5%) lower in extensive metabolizers and bioavailability was 33% (10.0% – 52.0%) higher compared to single dosing, which could be due to autoinhibition of CYP2C19. Esomeprazole pharmacokinetics during pregnancy appears to be more dependent on CYP3A4.
17 Feb 2022Submitted to British Journal of Clinical Pharmacology
22 Feb 2022Submission Checks Completed
22 Feb 2022Assigned to Editor
27 Feb 2022Reviewer(s) Assigned
15 Mar 2022Review(s) Completed, Editorial Evaluation Pending
21 Mar 2022Editorial Decision: Revise Minor
19 Apr 20221st Revision Received
20 Apr 2022Submission Checks Completed
20 Apr 2022Assigned to Editor
20 Apr 2022Review(s) Completed, Editorial Evaluation Pending
20 Apr 2022Reviewer(s) Assigned
05 May 2022Editorial Decision: Accept
03 Jun 2022Published in British Journal of Clinical Pharmacology. 10.1111/bcp.15416