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Pharmacokinetics of the most commonly used antihypertensive drugs throughout pregnancy methyldopa, labetalol, and nifedipine: a systematic review.
Eur J Clin Pharmacol. 2022 Nov; 78(11):1763-1776.EJ

Abstract

PURPOSE

Antihypertensive drugs are among the most prescribed drugs during pregnancy. Methyldopa, labetalol, and nifedipine have been perceived safe to use during pregnancy and are therefore recommended in international guidelines for treatment of hypertension. In this review, we provide a complete overview of what is known on the pharmacokinetics (PK) of the antihypertensive drugs methyldopa, labetalol, and nifedipine throughout pregnancy.

METHODS

A systematic search was performed to retrieve studies on the PK of methyldopa, labetalol, and nifedipine used throughout pregnancy. The search was restricted to English and original studies. The systematic search was conducted on July 27, 2021, in Embase, Medline Ovid, Web of Science, Cochrane Library, and Google Scholar. Keywords were methyldopa, labetalol, nifedipine, pharmacokinetics, pregnancy, and placenta.

RESULTS

A total of 1459 unique references were identified of which title and abstract were screened. Based on this screening, 67 full-text papers were assessed, to retain 30 PK studies of which 2 described methyldopa, 12 labetalol, and 16 nifedipine. No fetal accumulation is found for any of the antihypertensive drugs studied.

CONCLUSION

We conclude that despite decades of prescribing methyldopa, labetalol, and nifedipine throughout pregnancy, descriptions of their PK during pregnancy are hampered by a large heterogeneity in the low number of available studies. Aiming for evidence-based and personalized dosing of antihypertensive medication in the future, further studies on the relationship of both PK and pharmacodynamics (including the optimal blood pressure targeting) during pregnancy and pregnancy-related pathology are urgently needed to prevent undertreatment, overtreatment, and side effects.

Authors+Show Affiliations

Department of Internal Medicine, Division of Pharmacology and Vascular Medicine, Erasmus MC University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. Department of Clinical Pharmacy, Erasmus MC University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.Department of Clinical Pharmacy, Erasmus MC University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, The Netherlands.Obstetrics and Gynecology, Division Obstetrics and Prenatal Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands.Department of Clinical Pharmacy, Erasmus MC University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. Pediatrics, Division of Neonatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.Department of Internal Medicine, Division of Pharmacology and Vascular Medicine, Erasmus MC University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. Obstetrics and Gynecology, Division Obstetrics and Prenatal Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands.Department of Clinical Pharmacy, Erasmus MC University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. Department of Development and Regeneration, KU Leuven, Leuven, Belgium. Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.Department of Internal Medicine, Division of Pharmacology and Vascular Medicine, Erasmus MC University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. j.versmissen@erasmusmc.nl. Department of Clinical Pharmacy, Erasmus MC University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. j.versmissen@erasmusmc.nl.

Pub Type(s)

Journal Article
Review
Systematic Review

Language

eng

PubMed ID

36104450

Citation

van de Vusse, Dylan, et al. "Pharmacokinetics of the Most Commonly Used Antihypertensive Drugs Throughout Pregnancy Methyldopa, Labetalol, and Nifedipine: a Systematic Review." European Journal of Clinical Pharmacology, vol. 78, no. 11, 2022, pp. 1763-1776.
van de Vusse D, Mian P, Schoenmakers S, et al. Pharmacokinetics of the most commonly used antihypertensive drugs throughout pregnancy methyldopa, labetalol, and nifedipine: a systematic review. Eur J Clin Pharmacol. 2022;78(11):1763-1776.
van de Vusse, D., Mian, P., Schoenmakers, S., Flint, R. B., Visser, W., Allegaert, K., & Versmissen, J. (2022). Pharmacokinetics of the most commonly used antihypertensive drugs throughout pregnancy methyldopa, labetalol, and nifedipine: a systematic review. European Journal of Clinical Pharmacology, 78(11), 1763-1776. https://doi.org/10.1007/s00228-022-03382-3
van de Vusse D, et al. Pharmacokinetics of the Most Commonly Used Antihypertensive Drugs Throughout Pregnancy Methyldopa, Labetalol, and Nifedipine: a Systematic Review. Eur J Clin Pharmacol. 2022;78(11):1763-1776. PubMed PMID: 36104450.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetics of the most commonly used antihypertensive drugs throughout pregnancy methyldopa, labetalol, and nifedipine: a systematic review. AU - van de Vusse,Dylan, AU - Mian,Paola, AU - Schoenmakers,Sam, AU - Flint,Robert B, AU - Visser,Willy, AU - Allegaert,Karel, AU - Versmissen,Jorie, Y1 - 2022/09/15/ PY - 2022/06/02/received PY - 2022/09/03/accepted PY - 2022/9/15/pubmed PY - 2022/10/12/medline PY - 2022/9/14/entrez KW - Hypertension KW - Hypertensive disorders of pregnancy KW - Labetalol KW - Methyldopa KW - Nifedipine KW - Pharmacokinetics KW - Pregnancy SP - 1763 EP - 1776 JF - European journal of clinical pharmacology JO - Eur J Clin Pharmacol VL - 78 IS - 11 N2 - PURPOSE: Antihypertensive drugs are among the most prescribed drugs during pregnancy. Methyldopa, labetalol, and nifedipine have been perceived safe to use during pregnancy and are therefore recommended in international guidelines for treatment of hypertension. In this review, we provide a complete overview of what is known on the pharmacokinetics (PK) of the antihypertensive drugs methyldopa, labetalol, and nifedipine throughout pregnancy. METHODS: A systematic search was performed to retrieve studies on the PK of methyldopa, labetalol, and nifedipine used throughout pregnancy. The search was restricted to English and original studies. The systematic search was conducted on July 27, 2021, in Embase, Medline Ovid, Web of Science, Cochrane Library, and Google Scholar. Keywords were methyldopa, labetalol, nifedipine, pharmacokinetics, pregnancy, and placenta. RESULTS: A total of 1459 unique references were identified of which title and abstract were screened. Based on this screening, 67 full-text papers were assessed, to retain 30 PK studies of which 2 described methyldopa, 12 labetalol, and 16 nifedipine. No fetal accumulation is found for any of the antihypertensive drugs studied. CONCLUSION: We conclude that despite decades of prescribing methyldopa, labetalol, and nifedipine throughout pregnancy, descriptions of their PK during pregnancy are hampered by a large heterogeneity in the low number of available studies. Aiming for evidence-based and personalized dosing of antihypertensive medication in the future, further studies on the relationship of both PK and pharmacodynamics (including the optimal blood pressure targeting) during pregnancy and pregnancy-related pathology are urgently needed to prevent undertreatment, overtreatment, and side effects. SN - 1432-1041 UR - https://www.unboundmedicine.com/medline/citation/36104450/Pharmacokinetics_of_the_most_commonly_used_antihypertensive_drugs_throughout_pregnancy_methyldopa,_labetalol,_and_nifedipine:_a_systematic_review. DB - PRIME DP - Unbound Medicine ER -