Administration and Pharmacokinetics of Levothyroxine

Abstract

Lifelong treatment with LT4, guided by levels of thyrotropin, is the mainstay of management of hypothyroidism. The bioavailability of LT4 is about 70% following an oral dose, with absorption occurring mainly in the ileum and jejunum. Maximum plasma concentrations of LT4 are achieved about 3 h after an oral dose in patients with hypothyroidism. The long terminal half-life of orally administered LT4, about 7.5 days, is consistent with once-daily dosing. Pregnancy, several medical conditions (especially) those affecting the gut, and a number of drugs, supplements, or foodstuffs can reduce the absorption and absolute bioavailability of LT4, or can alter the secretion of TSH, with detrimental consequences for longterm control of thyroid function. Poor adherence to LT4 therapy is also a common challenge. The introduction of novel formulations of LT4, with more precise delivery of the active ingredient and higher levels of bioequivalence with existing products will facilitate accurate titration of LT4 for patients with hypothyroidism.

Refractory Hypothyroidism: Unraveling the Complexities of Diagnosis and Management

“…3,18 LT4 is predominantly absorbed in the jejunum and ileum, 3 with absorption rates of 70% to 80% when taken on an empty stomach, and reaching its peak concentration in approximately 3 h, with a bioavailability of 70% to 80%. 19 The complete mechanism of LT4 transport across the intestinal mucosa is not fully understood, but it appears to involve the participation of transmembrane proteins, such as the organic anion transporters family, Na-taurocholate cotransporter, amino acid transporters type L 1 and 2, and monocarboxylate transporters 8 and 10, which are responsible for the entry and exit of thyroxine (T4). 20 There may also be a paracellular pathway that contributes to the absorption of LT4.…”

Thyroid hormones mediate the impact of early-life stress on ventral tegmental area gene expression and behavior

“…We hypothesized that if thyroid dysfunction mediated the impact of ELS on hypersensitivity to later stress, rescue of thyroid signaling after ELS with levothyroxine treatment would ameliorate ELS-induced behavioral changes. Because mice showed short-term impairment of thyroid function after ELS that recovered by adolescence, and the half-life of LT4 is approximately 7 days (Lipp, 2021), we treated mice for only five days with LT4 in drinking water in order to prevent over-treatment. Consistent with previous findings (Peña et al, 2017(Peña et al, , 2019b, the combination of ELS and adult social defeat stress increased social avoidance in male mice, and to a lesser extent in female mice (Figure 2B-E).…”