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Levothyroxine, stable isotope, pharmacokinetics, pregnancy
Pharmacokinetic studies are conducted in order to determine drug absorption, distribution, metabolism and excretion. This knowledge serves to help determine the appropriate and timely use of medications and is also an important step in providing individualized therapeutics according to patient characteristics, such as disease state and genotypes of drug metabolizing enzymes. An innovative way of conducting pharmacokinetic research in pregnancy is presented, with the drug levothyroxine (LT4).
The stable, non-radioactive Carbon-13 isotope was used to prepare a derivative of LT4, which was then used to determine the pharmacokinetics of the drug in 9 pregnant women serving as their own controls. Of 9 study subjects, 6 returned to participate in the post partum (non-pregnant) portion of the study. The median time to peak blood level was determined to be at 8 hours post dose. The AUC0-? results were significantly higher during pregnancy than in the same woman approximately 6 months post partum. The increase in LT4 AUC during pregnancy could be attributed to a decrease in LT4 clearance. Additionally, a large variability in the pharmacokinetics of LT4 was found in pregnant women, and a relatively narrower range of variability in non-pregnant women. In order to solidify these findings, a larger group of patients is required. In addition, the mechanisms responsible for the gestational differences in pharmacokinetics need to be investigated.
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