Document Detail


Longitudinal comparison of thyroxine pharmacokinetics between pregnant and nonpregnant women: a stable isotope study.
MedLine Citation:
PMID:  20962709     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Offie P Soldin; Steven J Soldin; Alexander A Vinks; Islam Younis; Helain J Landy
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Therapeutic drug monitoring     Volume:  32     ISSN:  1536-3694     ISO Abbreviation:  Ther Drug Monit     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-11     Completed Date:  2011-02-28     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  7909660     Medline TA:  Ther Drug Monit     Country:  United States    
Other Details:
Languages:  eng     Pagination:  767-73     Citation Subset:  IM    
Affiliation:
Department of Medicine, Oncology, Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20057, USA. os35@georgetown.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Area Under Curve
Carbon Isotopes
Drug Administration Schedule
Female
Half-Life
Hormone Replacement Therapy
Humans
Hypothyroidism / blood*,  drug therapy
Longitudinal Studies
Pregnancy
Pregnancy Complications / blood*,  drug therapy
Tandem Mass Spectrometry
Thyroxine / administration & dosage,  pharmacokinetics*,  therapeutic use
Grant Support
ID/Acronym/Agency:
5U10HD037249-10/HD/NICHD NIH HHS; 5U10HD0478925/HD/NICHD NIH HHS; M01 RR023942/RR/NCRR NIH HHS; M01RR-023942/RR/NCRR NIH HHS; UL1 TR000101/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
0/Carbon Isotopes; 7488-70-2/Thyroxine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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