Authors: Lilja, Jari J.; Laitinen, Kalevi¹; Neuvonen, Pertti J.²

Source: British Journal of Clinical Pharmacology, Volume 60, Number 3, September 2005 , pp. 337-341(5)

Publisher: Wiley-Blackwell

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.

Keywords: food-drug interaction; grapefruit juice; levothyroxine

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2125.2005.02433.x

Affiliations: 1: Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland 2: Department of Clinical Pharmacology

Publication date: 2005-09-01

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