Longitudinal comparison of thyroxine pharmacokinetics between pregnant and nonpregnant women: a stable isotope study
Open accessAbstract
The treatment of maternal hypothyroidism presents clinicians with a unique challenge, because dosing regimens previously developed and validated for nonpregnant women cannot be easily extrapolated to dosing in pregnancy. Thyroid hormone requirement increases by 20% to 40% early during pregnancy, persisting throughout gestation. Accordingly, women with treated hypothyroidism need to increase their levothyroxine dose to prevent maternal hypothyroidism and the associated impaired cognitive development and increased fetal mortality. We investigated the pharmacokinetic properties of levothyroxine during pregnancy through the use of a novel, traceable form of levothyroxine. The objective was to conduct a longitudinal study to determine whether levothyroxine pharmacokinetics differ in the pregnant versus nonpregnant state. We used a unique C-levothyroxine-tracer method to distinguish between endogenous and exogenous levothyroxine and studied the pharmacokinetics of a single oral dose of levothyroxine using tandem mass spectrometry. Moreover, we were able to detect single dose amounts of the drug, in picogram/mL concentrations. The area under the curve was 23.0 ng*h/mL in pregnancy and 14.8 ng*h/mL in nonpregnant women (P < 0.03) with median serum half-lives of 32.1 hours and 24.1 hours, respectively (P < 0.04). Further research involves the measurement of free thyroxine on these samples using tandem mass spectrometry. Future work should focus on the mechanisms responsible for the gestational differences in pharmacokinetics and whether these should necessitate dose schedule changes in pregnancy.
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In hypothyroid women, levothyroxine dose may need to increase by up to 50% during the first trimester and remain at that level until delivery.
“In women with hypothyroidism, an up to 50% increase in LT4 dose is required during the first trimester, and this dose is maintained until delivery.55”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [55]
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A review of the pharmacokinetics of levothyroxine for the treatment of hypothyroidism
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“Women with treated hypothyroidism, accordingly, may need to increase their dose of levothyroxine to prevent hypothyroidism and its attendant adverse outcomes for pregnancy [61].”
BackgroundRefractory hypothyroidism: unraveling the complexities of diagnosis and management
Quiroz-Aldave, J. E., Concepción-Zavaleta, M. J., Durand-Vásquez, M. D. C., Concepción-Urteaga, L. A., Gamarra-Osorio, E. R., Suárez-Rojas, J., Rafael-Robles, L. D. P., Paz-Ibarra, J., & Román-González, A. (2023) · Endocrine Practice · doi:10.1016/j.eprac.2023.09.003 · Cited by 14 · see citing works
- Authors
- Soldin, O. P., Soldin, S. J., Vinks, A. A., Younis, I., & Landy, H. J.
- Affiliations
- Georgetown University Medical Center (US)
- Georgetown University (US)
- Cincinnati Children's Hospital Medical Center (US)
- United States Food and Drug Administration (US)
- Corresponding author
- Soldin, Offie P
- Venue
- Therapeutic Drug Monitoring
- Published
- 2010-12
- Volume
- 32
- Issue
- 6
- Pages
- 767-773
- ISSN
- 0163-4356 (ISSN-L)
- PMC
- PMC3622873
- OpenAlex
- W2005807097
- Cited by
- 9
- References
- 32
- Citations by year
- 2023: 1 · 2022: 1 · 2019: 1 · 2017: 2 · 2012: 2
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Therapeutic Drug Monitoring (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000101)
- National Center for Research Resources (M01RR023942)
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (5U10HD0478925, U10HD037249)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Keywords
- levothyroxine, pregnancy, maternal hypothyroidism, serum half-life, free thyroxine
- MeSH terms
- Adult, Carbon Isotopes, Drug Administration Schedule, Female, Half-Life, Humans, Hypothyroidism, Longitudinal Studies, Pregnancy, Pregnancy Complications, Thyroxine, Area Under Curve, Hormone Replacement Therapy, Tandem Mass Spectrometry
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