MedStar Authors catalog › Details for: Stable isotope pharmacokinetic studies provide insight into effects of age, sex, and weight on levothyroxine metabolism.
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Stable isotope pharmacokinetic studies provide insight into effects of age, sex, and weight on levothyroxine metabolism.

by Burman, Kenneth D.
Citation: Thyroid. 28(1):41-49, 2018 01..Journal: Thyroid : official journal of the American Thyroid Association.Published: ; 2018ISSN: 1050-7256.Full author list: Younis I; Ahmed MA; Burman KD; Soldin OP; Jonklaas J.UI/PMID: 29212434.Subject(s): Administration, Oral | Adult | Age Factors | Aged | *Body Weight/ph [Physiology] | Dose-Response Relationship, Drug | Female | Humans | *Hypothyroidism/dt [Drug Therapy] | Male | Metabolic Clearance Rate | Middle Aged | Sex Factors | *Thyroxine/pk [Pharmacokinetics] | Thyroxine/tu [Therapeutic Use] | Young AdultInstitution(s): MedStar Washington Hospital CenterDepartment(s): Medicine/EndocrinologyActivity type: Journal Article.Medline article type(s): Journal ArticleOnline resources: Click here to access online Digital Object Identifier: (Click here) Abbreviated citation: Thyroid. 28(1):41-49, 2018 01.Local Holdings: Available online from MWHC library: August 2000 - present, Available in print through MWHC library: 1999 - 2006.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 micro g (range 70 to 300 micro g). 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/micro g. The dose normalized AUC0-t and half-life of the terminal distribution phase were 0.931 ng.h/mL/micro g 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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