Effect of Age, Weight and Sex on Levothyroxine Pharmacokinetics

Study Overview
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Brief Summary
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This study was a prospective, single-center, open-label, non-randomized, pharmacokinetic study using stable isotope carbon-13 labeled levothyroxine

Detailed Description
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Setting The study was conducted on the clinical research unit of an academic medical center. Participants Adults of any age being treated with levothyroxine for hypothyroidism were studied. Interventions A single dose of 13C- LT4 was administered to hypothyroid subjects taking levothyroxine replacement. Main Outcomes and Measures Eighteen serial plasma samples were collected. One sample was obtained before the 13C- LT4 dose and the remainder over the 312-hour period post-dosing. 13C- LT4 concentration was quantified using validated liquid chromatography tandem mass spectrometry methods. Pharmacokinetic analysis was conducted using linear log trapezoidal non-compartmental analysis using Phoenix 6.4.

Official Title
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Hypothyroidism Treatment in Aging and Thyroid Cancer

Conditions
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Hypothyroidism Primary

Intervention / Treatment
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* Drug: Administration of stable Isotope labeled levothyroxine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age >21 years at the time of consent euthyroidism while undergoing treatment with LT4 no other serious illness ability to give written informed consent. Exclusion Criteria: baseline hematocrit lower than 28.0% TSH greater than 4.5 mIU/L kidney dysfunction concomitant use of drugs that affect thyroidal axis interactions

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Open label prospective study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stable isotope arm<br>Measurement of blood levels of labelled levothyroxine after administration of single oral dose of stable isotope levothyroxine | Drug: Administration of stable Isotope labeled levothyroxine<br>* Administration of single dose of stable isotope carbon-13 labeled levothyroxine and measurement of blood levels of stable isotope-labeled levothyroxine<br>* Other names: levothyroxine or synthroid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CL/F | oral clearance rate (defined as the ratio of dose administered to AUC0-∞) | 120 hours | 
| V/F | apparent volume of distribution (estimated by CL/F/ λ) | 120 hours | 
| t-half | the half-life of the terminal disposition phase (t-half) estimated by ln(2)/λ . | 120 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CL/F analysed by age groups | CL/F will be compared in adults (age ≤60 years) versus elderly (age>60 years) using Wilcoxon signed-rank test using significance level of α = 0.05. Additionally, these PK parameters were regressed against age (as a continuous covariate). Sex (male or female), weight (as a continuous covariate), and body mass index (BMI) (as a continuous covariate) will be considered using a stepwise linear regression approach. | 120 hours | 
| V/F analysed by age groups | V/F will be compared in adults (age ≤60 years) versus elderly (age>60 years) using Wilcoxon signed-rank test using significance level of α = 0.05. Additionally, these PK parameters were regressed against age (as a continuous covariate). Sex (male or female), weight (as a continuous covariate), and body mass index (BMI) (as a continuous covariate) will be considered using a stepwise linear regression approach. | 120 hours | 
| t-half by age groups | t-half will be compared in adults (age ≤60 years) versus elderly (age>60 years) using Wilcoxon signed-rank test using significance level of α = 0.05. Additionally, these PK parameters were regressed against age (as a continuous covariate). Sex (male or female), weight (as a continuous covariate), and body mass index (BMI) (as a continuous covariate) will be considered using a stepwise linear regression approach. | 120 hours |