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Effects of grapefruit juice on the absorption of levothyroxine.

Author(s): Lilja JJ, Laitinen K, Neuvonen PJ

Affiliation(s): Department of Clinical Pharmacology, University of Helsinki and Helsinki University Cental Hospital, Helsinki, Finland. jara.lilja@hus.fi

Publication date & source: 2005-09, Br J Clin Pharmacol., 60(3):337-41.

Publication type: Randomized Controlled Trial

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 microg 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.

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