Effect of levothyroxine administration on intestinal P‐glycoprotein expression: Consequences for drug disposition*

Abstract

Expression of intestinal P-glycoprotein in humans appears to be influenced by thyroid hormones. The functional consequences need to be addressed in patients with hyperthyroidism.

Long-term Levothyroxine Treatment Decreases the Oral Bioavailability of Cyclosporin A by Inducing P-glycoprotein in Small Intestine

“…It has also been reported that the expression of P-gp is induced in duodenum of LTX-treated volunteers. 9) These results may re‰ect the fact that the duodenum is the initial site of exposure after the p.o. administration of LTX, although CYP3A2 mRNA expression was not diŠerent among the tissues.…”

“…Siegmund et al 9) reported that, although the expression of P-gp in duodenum was increased 3.8-fold by LTX treatment, the change in P-gp expression was associated with only minor alterations in the half-life of talinolol after both oral and intravenous administration. However, in our case, the increase of about 2-fold in the duodenal expression of P-gp induced by LTX greatly decreased the bioavailability of CyA to about a quarter of that in the control rats ( Table 2).…”

“…7,8) Siegmund et al 9) found that the expression of P-glycoprotein (P-gp) was increased in duodenum after oral administration of levothyroxine (LTX, 200 mg W day) for 17 days in healthy volunteers, and the half life of talinolol, a substrate of P-glycoprotein, was slightly decreased. Recently, we have noted that the blood CyA concentration tends to be decreased in patients receiving oral immunotherapy with CyA in combination with LTX, in comparison with similar patients not receiving LTX (Fig.…”

Levothyroxine Up-Regulates P-Glycoprotein Independent of the Pregnane X Receptor

“…In a previous study (Siegmund et al, 2002), P-glycoprotein levels were increased in duodenal biopsy specimens from healthy human volunteers after administration of levothyroxine (L-T 4 ). However, the increase in ABCB1 mRNA levels was not statistically significant.…”

Determination of P-Glycoprotein ATPase Activity Using Luciferase

“…Siegmund et al reported that P-gp mRNA expression and immunoreactive P-gp in the duodenums of healthy volunteers were increased after administration of levothyroxine. 19) Although obtained from human colorectal cancer, the Caco-2 cell line is capable of morphological and biochemical differentiation in vitro to form intestinal epithelia under normal culture conditions. 20) Transcript levels of ABC transporters except for breast cancer-related protein (BCRP) show a good correlation between jejunum and Caco-2 cells.…”