Send to

Choose Destination
Drug Metab Pharmacokinet. 2005 Oct;20(5):324-30.

Long-term levothyroxine treatment decreases the oral bioavailability of cyclosporin A by inducing P-glycoprotein in small intestine.

Author information

Department of Clinical Pharmacy, Graduate School of Natural Science and Technology, Kanazawa University, Takara-machi, Japan.


We have noticed that the trough level of blood concentration of cyclosporin A (CyA) tends to be lower in patients receiving long-term oral levothyroxine (LTX) than in patients not receiving LTX. We confirmed this clinical observation in experiments using Wistar rats orally given LTX (8 microg/kg) or saline (control) for 3 weeks, followed by CyA (10 mg/kg). The LTX treatment had little effect on the blood concentrations of CyA after i.v. administration, whereas they were decreased significantly after p.o. administration. After p.o. administration, the value of the area under the blood concentration-time curve from 0 to 24 hr and the bioavailability of CyA in the LTX group were decreased to only about one-fifth and a quarter of those in the control group, respectively. After treatment with LTX, the expression levels of mdr1a, mdr1b and CYP3A2 mRNAs in the duodenum were markedly increased to about twice the control, but in jejunum, ileum and liver the expression levels were little changed. These findings suggest that the absorption of CyA, which occurs mainly from the upper intestine, is reduced as a result of efflux transport via P-glycoprotein induced by LTX. In conclusion, careful monitoring of CyA levels is required in the event of LTX administration to patients receiving immunotherapy with CyA.

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for J-STAGE, Japan Science and Technology Information Aggregator, Electronic
Loading ...
Support Center