Population pharmacokinetics of esomeprazole in patients with preterm preeclampsia.

Autor: Gebreyesus MS; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa., Decloedt EH; Division of Clinical Pharmacology, Department of Medicine, Stellenbosch University and Tygerberg Hospital, Stellenbosch, South Africa., Cluver CA; Department of Obstetrics and Gynaecology, Stellenbosch University and Tygerberg Hospital, Stellenbosch, South Africa., Hunfeld NGM; Department of Pharmacy and Intensive Care, Erasmus University Rotterdam, Rotterdam., Helgadóttir H; Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Iceland, Reykjavik, Iceland., Björnsson ES; Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Iceland, Reykjavik, Iceland., Wasmann RE; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa., Denti P; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Jazyk: angličtina
Zdroj: British journal of clinical pharmacology [Br J Clin Pharmacol] 2022 Oct; Vol. 88 (10), pp. 4639-4645. Date of Electronic Publication: 2022 Jun 03.
DOI: 10.1111/bcp.15416
Abstrakt: Esomeprazole is a proton pump inhibitor being investigated for treatment of preeclampsia. Esomeprazole pharmacokinetics during pregnancy are unknown. We used data from 10 pregnant participants with preterm preeclampsia, and 49 non-pregnant participants to develop a population pharmacokinetic model of esomeprazole. A two-compartment model described the data well. In pregnant participants after single dose, clearance was 42.2% (14.9-61.6%) lower compared to non-pregnant, most likely due to inhibition of CYP2C19. In non-pregnant participants 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. During pregnancy, the CYP2C19 autoinhibition effect with repeated dosing is expected to lead to much lower increase in exposure compared to non-pregnant individuals, since CYP2C19 is already inhibited due to pregnancy.
(© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)
Databáze: MEDLINE
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