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Stable Isotope Pharmacokinetic Studies Provide Insight into Effects of Age, Sex, and Weight on Levothyroxine Metabolism.

ABSTRACT: BACKGROUND:This study sought to determine whether levothyroxine pharmacokinetics (PKs) are affected by age, weight, and sex. METHODS:A PK 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 22-78 years) and median weight of 65.9 kg (range 50-150 kg) were enrolled in the study. The median 13C-LT4 dose administered was 100 μg (range 70-300 μg). The median oral clearance rate (CL/F), apparent volume of distribution (V/F), time to peak concentration (Tmax), and dose-normalized peak concentration (Cmax) of 13C-LT4 were estimated to be 0.712 L/h, 164.9 L, 4 h, and 7.5 ng/L/μg, respectively. The dose-normalized area under the concentration-time curve from time 0 to 120 hours 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 aged >60 years (n = 10) and patients aged ≤60 years (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.

SUBMITTER: Younis IR

PROVIDER: S-EPMC5770123 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Stable Isotope Pharmacokinetic Studies Provide Insight into Effects of Age, Sex, and Weight on Levothyroxine Metabolism.

Younis Islam R IR Ahmed Mariam A MA Burman Kenneth D KD Soldin Offie P OP Jonklaas Jacqueline J

Thyroid : official journal of the American Thyroid Association 20180102 1

<h4>Background</h4>This study sought to determine whether levothyroxine pharmacokinetics (PKs) are affected by age, weight, and sex.<h4>Methods</h4>A PK study was performed after administration of a tracer dose of carbon-13-labeled LT4 (<sup>13</sup>C-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 <sup>13</sup>C-LT4 was administered. Eighteen serial plasma samples were ...[more]

PMID: 29212434

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Stable Isotope Pharmacokinetic Studies Provide Insight into Effects of Age, Sex, and Weight on Levothyroxine Metabolism.

Publications

Stable Isotope Pharmacokinetic Studies Provide Insight into Effects of Age, Sex, and Weight on Levothyroxine Metabolism.

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