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Singh N, Singh PN, Hershman JM. Effect of Calcium Carbonate on the Absorption of Levothyroxine. JAMA. 2000;283(21):2822–2825. doi:10.1001/jama.283.21.2822
Author Affiliations: Division of Endocrinology and Metabolism, VA Greater Los Angeles Healthcare System, UCLA School of Medicine, Los Angeles, Calif (Drs N. Singh and Hershman), and Division of Epidemiology, Loma Linda Medical Center, Loma Linda, Calif (Dr P. Singh).
Context The effect of calcium carbonate on the absorption of levothyroxine has
not been studied systematically. Such a potential drug interaction merits
investigation because concurrent treatment with both drugs is common, particularly
in postmenopausal women.
Objective To investigate the potential interference of calcium carbonate in the
absorption of levothyroxine.
Design Prospective cohort study conducted from November 1998 to June 1999,
supplemented with an in vitro study of thyroxine (T4) binding to
Setting Veterans Affairs Medical Center in West Los Angeles, Calif.
Patients Twenty patients (age range, 27-78 years; n=11 men) with hypothyroidism
who were taking a stable long-term regimen of levothyroxine were included
in the study. All patients had serum free T4 and thyrotropin values
in the normal range before beginning the study.
Intervention Subjects were instructed to take 1200 mg/d of elemental calcium as calcium
carbonate, ingested with their levothyroxine, for 3 months.
Main Outcome Measures Levels of free T4, total T4, total triiodothyronine
(T3), and thyrotropin, measured in all subjects at baseline (while
taking levothyroxine alone), at 2 and 3 months (while taking calcium carbonate
and levothyroxine), and 2 months after calcium carbonate discontinuation (while
continuing to take levothyroxine).
Results Mean free T4 and total T4 levels were significantly
reduced during the calcium period and increased after calcium discontinuation.
Mean free T4 levels were 17 pmol/L (1.3 ng/dL) at baseline, 15
pmol/L (1.2 ng/dL) during the calcium period, and 18 pmol/L (1.4 ng/dL) after
calcium discontinuation (overall P<.001); mean
total T4 levels were 118 nmol/L (9.2 µg/dL) at baseline,
111 nmol/L (8.6 µg/dL) during the calcium period, and 120 nmol/L (9.3
µg/dL) after calcium discontinuation (overall P=.03).
Mean thyrotropin levels increased significantly, from 1.6 mIU/L at baseline
to 2.7 mIU/L during the calcium period, and decreased to 1.4 mIU/L after calcium
discontinuation (P=.008). Twenty percent of patients
had serum thyrotropin levels higher than the normal range during the calcium
period; the highest observed level was 7.8 mIU/L. Mean T3 levels
did not change during the calcium period. The in vitro study of T4
binding to calcium showed that adsorption of T4 to calcium carbonate
occurs at acidic pH levels.
Conclusions This study of 20 patients receiving long-term levothyroxine replacement
therapy indicates that calcium carbonate reduces T4 absorption
and increases serum thyrotropin levels. Levothyroxine adsorbs to calcium carbonate
in an acidic environment, which may reduce its bioavailability.
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