Labetalol Dosing in Pregnancy: PBPK/PD and CYP2C19 Polymorphisms.
Autor: | Liu XI; Division of Clinical Pharmacology, Children's National Hospital, Washington, DC, USA., Green DJ; Office of Pediatric Therapeutics, US Food and Drug Administration, Silver Spring, MD, USA., van den Anker J; Division of Clinical Pharmacology, Children's National Hospital, Washington, DC, USA., Calderon J; Division of Maternal-Fetal Medicine, Department of OB/Gyn, George Washington University, Washington, DC, USA., Ahmadzia H; Division of Maternal-Fetal Medicine, Department of OB/Gyn, George Washington University, Washington, DC, USA., Burckart GJ; Office of Clinical Pharmacology, US Food and Drug Administration, Silver Spring, MD, USA., Dallmann A; Bayer HealthCare SAS, Loos, France, on behalf of: Pharmacometrics/Modeling & Simulation, Research & Development, Pharmaceuticals, Bayer, AG, Germany. |
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Jazyk: | angličtina |
Zdroj: | Journal of clinical pharmacology [J Clin Pharmacol] 2024 Jul 08. Date of Electronic Publication: 2024 Jul 08. |
DOI: | 10.1002/jcph.2496 |
Abstrakt: | As detailed information on the pharmacokinetics (PK) of labetalol in pregnant people are lacking, the aims of this study were: (1) to build a physiologically based PK (PBPK) model of labetalol in non-pregnant individuals that incorporates different CYP2C19 genotypes (specifically, *1/*1, *1/*2 or *3, *2/*2, and *17/*17); (2) to translate this model to the second and third trimester of pregnancy; and (3) to combine the model with a previously published direct pharmacodynamic (PD) model to predict the blood pressure lowering effect of labetalol in the third trimester. Clinical data for model evaluation was obtained from the scientific literature. In non-pregnant populations, the mean ratios of simulated versus observed peak concentration (C (© 2024, The American College of Clinical Pharmacology.) |
Databáze: | MEDLINE |
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