Effect of Age, Weight and Sex on Levothyroxine Pharmacokinetics

Early Phase 1CompletedNCT03102177

Georgetown University41 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Hypothyroidism Primary

Interventions

Administration of stable Isotope labeled levothyroxineDRUG

Administration of single dose of stable isotope carbon-13 labeled levothyroxine and measurement of blood levels of stable isotope-labeled levothyroxine

Eligibility

Sex: ALLMin age: 21 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

CL/F

oral clearance rate (defined as the ratio of dose administered to AUC0-∞)

Time frame: 120 hours

V/F

apparent volume of distribution (estimated by CL/F/ λ)

Time frame: 120 hours

t-half

the half-life of the terminal disposition phase (t-half) estimated by ln(2)/λ .

Time frame: 120 hours

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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