Pharmacokinetics of L-Triiodothyronine in Patients Undergoing Thyroid Hormone Therapy Withdrawal
Autor: | Sheila Smith, Joyce D. Linderman, Van Tassell B, Wohlford Gf th, Francesco S. Celi, Sahzene Yavuz, F. M. Pucino |
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Rok vydání: | 2019 |
Předmět: |
Adult
Male endocrine system medicine.medical_specialty Combination therapy Hormone Replacement Therapy Endocrinology Diabetes and Metabolism medicine.medical_treatment Levothyroxine Thyrotropin 030209 endocrinology & metabolism Gastroenterology 03 medical and health sciences Deprescriptions 0302 clinical medicine Endocrinology Hypothyroidism Pharmacokinetics Internal medicine medicine Humans In patient Thyroid Neoplasms Radionuclide Imaging Thyroid cancer L-Triiodothyronine business.industry Thyroid Middle Aged medicine.disease Thyroxine medicine.anatomical_structure 030220 oncology & carcinogenesis Thyroidectomy Triiodothyronine Female Hormone therapy business Thyroid Dysfunction: Hypothyroidism Thyrotoxicosis and Thyroid Function Tests medicine.drug |
Zdroj: | Thyroid |
ISSN: | 1557-9077 1050-7256 |
Popis: | Background: L-triiodothyronine (LT3) is a substitute for levothyroxine (LT4) for thyroid cancer (TC) patients during the preparation for nuclear medicine procedures, and it is used in combination with LT4 in patients who do not respond to the standard treatment for hypothyroidism. This therapy is commonly done by using fixed doses, potentially resulting in supraphysiologic levels of triiodothyronine (T3). A good understanding of the LT3 pharmacokinetics (PK) is necessary to design combination treatment schemes that are able to maintain serum T3 levels within the reference range, but data on the PK of LT3 are conflicting. Here, we present a study designed to characterize the PK of LT3 in patients devoid of endogenous thyroid hormone production, and not receiving LT4 therapy. Methods: We performed an open-label, PK study in patients undergoing thyroid hormone withdrawal in preparation for nuclear medicine procedures for the evaluation and treatment of follicular-derived TC. LT3 was substituted for LT4 at a 1:3 mcg/mcg dosage ratio thrice daily for at least 30 days. PK of the last LT3 dose while at steady state and terminal elimination was assessed over 11 days. Thereafter, a PK study was performed following the nuclear medicine procedure in patients who volunteered for a second study. Results: Fourteen patients age 48.5 ± 16.0 years completed the last dose study and five completed the second PK study. PK analysis indicates a time to maximum serum concentration of 1.8 ± 0.32 hours and two distinct phases of linear elimination, with a fast distribution phase and slow elimination phases with half-lives of 2.3 ± 0.11 hours and 22.9 ± 7.7 hours, supporting a two-compartment model. PK modeling predicts that a twice-daily administration of low-dose LT3 (0.07 mcg/kg twice daily) in combination with LT4 can predictably increase the serum T3 concentration without significant peaks above the reference range. Conclusions: The PK of LT3 is well described by a two-compartment model that assumes elimination only from the sampling compartment, with a rapid distribution phase and a slow elimination phase. This information will contribute to design therapeutic strategies for LT3/LT4 combination therapies directed to maintain stable T3 serum levels. |
Databáze: | OpenAIRE |
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