Effects of grapefruit juice on the absorption of levothyroxine

ABSTRACT

 

Aims

Our aim was to study the effect of grapefruit juice on the pharmacokinetics of levothyroxine.

 

Methods

In a randomized cross-over study with two phases, 10 healthy subjects ingested 200 ml grapefruit juice or water (control) three times daily for 2 days. On day 3, a single 600 µg dose of levothyroxine was administered with 200 ml grapefruit juice or water, which was also ingested 1 h before and 1 h after levothyroxine. Serum concentrations of total thyroxine (T4) and thyroid-stimulating hormone (TSH) were measured up to 24 h.

 

Results

Grapefruit juice decreased slightly (11%; P < 0.01) the maximal increase of T4 concentration after ingestion of levothyroxine from 66.4 nmol l⁻¹ to 59.4 nmol l⁻¹ (95% CI on the difference −11.3, −2.7). The incremental areas under the serum T4 concentration-time curve (dAUC) during the first 4 and 6 h were also decreased slightly: dAUC(0,4 h) by 13% (P < 0.05), from 195 nmol l⁻¹ h to 169 nmol l⁻¹ h (95% CI −51, −1) and dAUC(0,6 h) by 9% (P = 0.085), from 298 nmol l⁻¹ h to 271 nmol l⁻¹ h (95% CI −58, 4). The decrease in the serum concentration of TSH (1.25 mU l⁻¹) measured 24 h after ingestion of levothyroxine, was not altered by grapefruit juice.

 

Conclusions

Grapefruit juice may slightly delay the absorption of levothyroxine, but it seems to have only a minor effect on its bioavailability. Accordingly, the clinical relevance of the grapefruit juice-levothyroxine interaction is likely to be small.