Impaired Pharmacokinetics of Levothyroxine in Severely Obese Volunteers.

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Thyroid.

2011 Mar 21. [Epub ahead of print]

Impaired

Pharmacokinetics of Levothyroxine in Severely Obese Volunteers.

Michalaki

MA, Gkotsina

MI, Mamali

I, Markantes

GK, Faltaka

A, Kalfarentzos

F, Vagenakis

AG, Markou

KB.

1 Division of

Endocrinology, Department of Internal Medicine; University Hospital of Patras ,

Patras, Greece .

Abstract

Background:

Suppressive or replacement doses of levothyroxine (LT4) are affected by the

rate and extent of the active ingredient absorbed, as well as by the lean body

mass. Obesity has reached epidemic proportions worldwide and is related with

many comorbidities. The aim of this study was to determine the pharmacokinetic

parameters of LT4 in severely obese individuals and compared them with similar

data in lean control subjects. Methods: We studied 62 euthyroid subjects who

had negative tests for anti-thyroid peroxidise antibodies (Ab-TPO). Thirty

eight of these subjects were severely obese but otherwise healthy (severe obese

subjects [sOS] group). Twenty-four were healthy control subjects (control

group), with a body mass index of 23.3 ± 1.7 kg/m(2). Subjects received 600 μg oral sodium LT4

after an overnight fast. Serum triiodothyronine (T3), T4, and

thyroid-stimulating hormone were measured at baseline. Serum T4 and T3 was

measured 0.5, 1, 1.5, 2, 2.5, 3, and 4 hours after LT4 administration. Results:

Baseline serum T4 and thyroid-stimulating hormone concentrations were higher in

the SOS group than in the control group; serum T3 was similar in the two

groups. The corrected area under the curve and the maximum T4 concentration

after LT4 administration were lower, whereas the time to maximum concentration

from the baseline was higher in SOS than in the control group. The estimated

plasma volume was higher in the SOS than in the control group. Mean serum T3

levels increased gradually during the four hours after LT4 administration in

the control group. In contrast, they decreased gradually in the SOS group.

Conclusions: Severely obese individuals may need higher LT4 suppressive or

replacement doses than normal-weight individuals due, among other factors, to

impaired LT4 pharmacokinetic parameters. The latter could be attributed to

their higher plasma volume and/or to delayed gastrointestinal LT4 absorption.

T4 conversion to T3 might be defective in severe obesity.

PMID: 21417917 [PubMed

- as supplied by publisher]