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Stable isotope pharmacokinetic studies provide insight into effects of age, sex, and weight on levothyroxine metabolism.

Stable isotope pharmacokinetic studies provide insight into effects of age, sex, and weight on levothyroxine metabolism.
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Younis I, Ahmed MA, Burman KD, Soldin OP, Jonklaas J,


Younis I, Ahmed MA, Burman KD, Soldin OP, Jonklaas J, (click to view)

Younis I, Ahmed MA, Burman KD, Soldin OP, Jonklaas J,

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Thyroid : official journal of the American Thyroid Association 2017 12 06() doi 10.1089/thy.2017.0380

Abstract

Background We wished to determine whether levothyroxine pharmacokinetics (PKs) are affected by age, weight, and sex. Methods A pharmacokinetic study was performed after administration of a tracer dose of carbon-13- labeled LT4 (13C-LT4). The study was conducted at an academic medical center. Adults of any age being treated with levothyroxine for hypothyroidism were enrolled in the study. A single dose of 13C- LT4 was administered. Eighteen serial plasma samples were collected. One sample was obtained before the 13C- LT4 dose and the majority of the remaining samples were collected over the 120-hour period post-dosing. 13C- LT4 concentration was quantified using liquid chromatography tandem mass spectrometry. PK analysis was conducted using a linear log trapezoidal non-compartmental analysis using Phoenix 6.4. Results Eight males and 33 females with a median age of 50 years (range 22 to 78 years) and median weight of 65.9 Kg (range 50 to 150 Kg) were enrolled in the study. The median 13C- LT4 dose administered was 100 µg (range 70 to 300 µg). The median CL/F, V/F, Tmax, and dose normalized Cmax of 13C- LT4 were estimated to be: 0.712 L/h, 164.9 L, 4 h, and 7.5 ng/L/µg. The dose normalized AUC0-t and half-life of the terminal distribution phase were 0.931 ng.h/mL/µg and 172.2 h respectively. There was no significant difference in any 13C- LT4 PK parameter between patients older than 60 years of age (n=10) and patients aged 60 years and younger (n= 31), nor was there a relationship between age as a continuous variable and 13C- LT4 PK parameters. Sex only affected CL/F, V/F, and dose normalized Cmax in univariate analyses. However, after adjusting for weight, sex was no longer a significant covariate. Weight was a significant predictor for CL/F, V/F and dose normalized Cmax of 13C- LT4 in multivariate analyses. Conclusion Prior studies suggest that patient age affects levothyroxine dose requirement. This study did not identify an effect of age and suggests that age-related changes in levothyroxine pharmacokinetics may be mediated by age-related weight differences. Physicians should consider a patient’s weight, rather than age, for estimating levothyroxine dosage requirement.

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