Ciprofloxacin and Rifampin have opposite effects on levothyroxine absorption
Abstract
BACKGROUND: Levothyroxine (L-T4) absorption varies between individuals, and can be affected by various concomitantly administered drugs. Case reports have indicated an association between cotreatment with ciprofloxacin or rifampin and hypothyroidism in patients on a stable L-T4 dose. METHODS: The effects of two antibiotics on T4 absorption were prospectively assessed in a double-blind, randomized, crossover fashion. Eight healthy volunteers received 1000 μg L-T4 combined with placebo, ciprofloxacin 750 mg, or rifampin 600 mg as single doses. We measured total plasma thyroxine (T4) concentrations over a 6-hour period after dosing using liquid chromatography-tandem mass spectrometry. For each study arm, areas under the T4 plasma concentration-time curve (T4 AUCs) were compared. RESULTS: Coadministration of ciprofloxacin significantly decreased the T4 AUC by 39% (p = 0.035), while, surprisingly, rifampin significantly increased T4 AUC by 25% (p = 0.003). CONCLUSION: Intestinal absorption of L-T4 is differentially affected by acute coadministration of ciprofloxacin or rifampin. Mechanistic studies focused on intestinal and possibly hepatic thyroid hormone transporters are required to explain the observed drug interactions with L-T4.
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Rifampicin increases LT4 bioavailability.
“in contrast to rifampicin, an antibiotic used to treat several bacterial infections, including tuberculosis, which increases LT4 bioavailability (81).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [81]
Ciprofloxacin has been reported to interfere with the intestinal transport of thyroxine, leading to decreased LT4 bioavailability.
“Ciprofloxacin is a quinolone antibiotic that has been reported to interfere with the intestinal transport of thyroxine, leading to decreased LT4 bioavailability”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [81]
Some drugs (eg, ciprofloxacin, rifampicin, and chromium picolinate) and grapefruit juice alter intestinal mucosal transporters, including the monocarboxylate transporter family and organic anion transporting polypeptides.
“In addition, some drugs (eg, ciprofloxacin, rifampicin, and chromium picolinate) and grapefruit juice alter intestinal mucosal transporters, including the monocarboxylate transporter family and organic anion transporting polypeptides (81–83).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [81]
Concomitant administration of ciprofloxacin was associated with significantly lower area under the plasma T4 concentration-time curve.
“Goldberg et al. showed that concomitant administration of ciprofloxacin was associated with a significantly lower area under the plasma T4 concentration–time curve [ 71 ].”
From Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults (2022) · cites this paper as [71]
Concomitant administration of rifampin and LT4 was associated with a significantly higher area under the plasma T4 concentration-time curve.
“In Goldberg et al. pharmacokinetic study, for example, the concomitant administration of rifampin and LT4 was associated with a significantly higher area under the plasma T4 concentration–time curve [ 71 ].”
From Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults (2022) · cites this paper as [71]
Cites
Halestrap, A. P., & Meredith, D. (2004) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-003-1067-2 · Cited by 1,054 · see citing works
Hilgendorf, C., Ahlin, G., Seithel‐Keuth, A., Artursson, P., Ungell, A.-L. B., & Karlsson, J. E. (2007) · Drug Metabolism and Disposition · doi:10.1124/dmd.107.014902 · Cited by 583 · see citing works
Transporters and drug therapy: Implications for drug disposition and disease
Ho, R. H., & KIM, R. (2005) · Clinical Pharmacology & Therapeutics · doi:10.1016/j.clpt.2005.05.011 · Cited by 502 · see citing works
Self-citationPRICE, T. N., JACKSON, N. V., & HALESTRAP, P. A. (1998) · Biochemical Journal · doi:10.1042/bj3290321 · Cited by 361 · see citing works
Basaria, S. S., & Cooper, D. S. (2005) · The American Journal of Medicine · doi:10.1016/j.amjmed.2004.11.028 · Cited by 341 · see citing works
Lau, Y. Y., Huang, Y. L., Frassetto, L. A., & Benet, L. Z. (2006) · Clinical Pharmacology & Therapeutics · doi:10.1038/sj.clpt.6100038 · Cited by 327 · see citing works
Tirona, R. G., Leake, B. F., Wolkoff, A. W., & Kim, R. B. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.043026 · Cited by 324 · see citing works
Self-citationIncreased need for thyroxine in women with hypothyroidism during estrogen therapy
Arafah, B. M. (2001) · New England Journal of Medicine · doi:10.1056/nejm200106073442302 · Cited by 267 · see citing works
Drugs that suppress TSH or cause central hypothyroidism
Haugen, B. R. (2009) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2009.08.003 · Cited by 252 · see citing works
Tissue-specific mRNA expression profiles of human solute carrier transporter superfamilies
Nishimura, M., & Naito, S. (2008) · Drug Metabolism and Pharmacokinetics · doi:10.2133/dmpk.23.22 · Cited by 190 · see citing works
Cellular entry of thyroid hormones by organic anion transporting polypeptides
Hagenbuch, B. (2007) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2007.03.004 · Cited by 135 · see citing works
van der Deure, W. M., Peeters, R. P., & Visser, T. J. (2010) · Journal of Molecular Endocrinology · doi:10.1677/jme-09-0042 · Cited by 130 · see citing works
Kappers, M. H. W., van Esch, J. H. M., Smedts, F. M. M., de Krijger, R. R., Eechoute, K., Mathijssen, R. H. J., Sleijfer, S., Leijten, F. P. J., Danser, A. H. J., van den Meiracker, A. H., et al. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1172 · Cited by 104 · see citing works
Hays, M. T. (1988) · Endocrine Research · doi:10.3109/07435808809032986 · Cited by 94 · see citing works
New medications which decrease levothyroxine absorption
John-Kalarickal, J., Pearlman, G., & Carlson, H. E. (2007) · Thyroid · doi:10.1089/thy.2007.0060 · Cited by 82 · see citing works
Effects of grapefruit juice on the absorption of levothyroxine
Lilja, J. J., Laitinen, K., & Neuvonen, P. J. (2005) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2005.02433.x · Cited by 74 · see citing works
Heuer, H., & Visser, T. J. (2013) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2012.04.009 · Cited by 64 · see citing works
Expression of LAT1 and LAT2 amino acid transporters in human and rat intestinal epithelial cells
Fraga, S., Pinho, M. J., & Soares-da-Silva, P. (2005) · Amino Acids · doi:10.1007/s00726-005-0221-x · Cited by 60 · see citing works
The effect of antipyrine, phenobarbitol and rifampicin on thyroid hormone metabolism in man
OHNHAUS, E. E., BÜRGI, H., BURGER, A., & STUDER, H. (1981) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.1981.tb02000.x · Cited by 50 · see citing works
Thyroid hormone export from cells: contribution of P-glycoprotein
Mitchell, A. M., Tom, M., & Mortimer, R. H. (2005) · Journal of Endocrinology · doi:10.1677/joe.1.06096 · Cited by 49 · see citing works
Arakawa, H., Shirasaka, Y., Haga, M., Nakanishi, T., & Tamai, I. (2012) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.1809 · Cited by 48 · see citing works
ISLEY, W. L. (1987) · Annals of Internal Medicine · doi:10.7326/0003-4819-107-4-517 · Cited by 46 · see citing works
U.S. Food and Drug Administration's Decision Regarding Bioequivalence of Levothyroxine Sodium
American Thyroid Association, T. E. S. (2004) · Thyroid · doi:10.1089/1050725041517138 · Cited by 44 · see citing works
zu Schwabedissen, H. E. M., Ware, J. A., Finkelstein, D., Chaudhry, A. S., Mansell, S. E., Leon‐Ponte, M., Strom, S. C., Zaher, H., Schwarz, U. I., Freeman, D. J., et al. (2011) · Hepatology · doi:10.1002/hep.24391 · Cited by 27 · see citing works
Self-citationCiprofloxacin interacts with thyroid replacement therapy
Cooper, J. G., Harboe, K., Frost, S. K., & Skadberg, Ø. (2005) · BMJ · doi:10.1136/bmj.330.7498.1002 · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Gastrointestinal malabsorption of thyroxine
Virili, C., Antonelli, A., Santaguida, M. G., Benvenga, S., & Centanni, M. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00168 · Cited by 164 · see citing works
Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review
Skelin, M., Lucijanić, T., Amidžić Klarić, D., Rešić, A., Bakula, M., Liberati-Čizmek, A.-M., Gharib, H., & Rahelić, D. (2017) · Clinical Therapeutics · doi:10.1016/j.clinthera.2017.01.005 · Cited by 133 · see citing works
New Formulations of Levothyroxine in the Treatment of Hypothyroidism: Trick or Treat?
Nagy, E. V., Perros, P., Papini, E., Katkó, M., & Hegedűs, L. D. (2020) · Thyroid · doi:10.1089/thy.2020.0515 · Cited by 65 · see citing works
Levothyroxine: conventional and novel drug delivery formulations.
Liu, H., Li, W., Zhang, W., Sun, S., & Chen, C. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnac030 · Cited by 63 · see citing works
Caron, P., Grunenwald, S., Persani, L., Borson-Chazot, F., Leroy, R., & Duntas, L. (2022) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-021-09691-9 · Cited by 53 · see citing works
Centanni, M., Duntas, L., Feldt-Rasmussen, U., Koehrle, J., Peeters, R. P., Razvi, S., Trimboli, P., & Virili, C. (2025) · European Thyroid Journal · doi:10.1530/etj-25-0123 · Cited by 38 · see citing works
“…is a quinolone antibiotic that has been reported to interfere with the intestinal transport of thyroxine, leading to decreased LT4 bioavailability, in contrast to rifampicin, an antibiotic used to treat several bacterial infections, including tuberculosis, which increases LT4 bioavailability (81).”
Medications and Food Interfering with the Bioavailability of Levothyroxine: A Systematic Review
Liu, H., Lu, M., Hu, J., Fu, G., Feng, Q., Sun, S., & Chen, C. (2023) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s414460 · Cited by 29 · see citing works
zu Schwabedissen, H. E. M., Ferreira, C., Schaefer, A. M., Oufir, M., Seibert, I., Hamburger, M. O., & Tirona, R. G. (2018) · Molecular Pharmacology · doi:10.1124/mol.117.111161 · Cited by 28 · see citing works
Self-citationDrug–Drug Interactions in Nosocomial Infections: An Updated Review for Clinicians
Hîncu, S., Apetroaei, M.-M., Ștefan, G., Fâcă, A. I., Arsene, A. L., Mahler, B., Drăgănescu, D., Tăerel, A.-E., Stancu, E., Hîncu, L., et al. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16091137 · Cited by 10 · see citing works
Thyroid Hormones, Iodine and Iodides, and Antithyroid Drugs
Mody, V. V., Singh, A. N., Deshmukh, R. R., & Shah, S. (2015) · Side effects of drugs annual · doi:10.1016/bs.seda.2015.08.007 · Cited by 10 · see citing works
Ngan, T. T., Tra, D. H., Mai, N. T. Q., Dung, H. V., Khai, N. V., Linh, P. V., & Phương, N. T. T. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1415206 · Cited by 5 · see citing works
Evaluation of evening versus morning levothyroxine intake in elderly (MONIALE)
Giassi, K. D. S., Piccoli, V., Rodrigues, T. D. C., & de Mello, R. G. B. (2019) · Trials · doi:10.1186/s13063-019-3816-3 · Cited by 5 · see citing works
Thyroid hormones, iodine and iodides, and antithyroid drugs
Ling, H., Patel, A., Park, J., & Bhave, V. (2019) · Side effects of drugs annual · doi:10.1016/bs.seda.2019.07.019 · Cited by 4 · see citing works
Clinical Practice Recommendations for Assessment and Management of Hypothyroidism
Alsifri, S. N., Aljuhani, N. R., Al-Jedai, A. H., Nasser, T., Alsabaan, F., Almudaiheem, H., Amir, A., Baissa, E., Ghannam, N., Aldawish, M., et al. (2022) · International Journal of Clinical Medicine · doi:10.4236/ijcm.2022.1312046 · Cited by 4 · see citing works
Thyroid hormones, Iodine and Iodides, and Antithyroid Drugs
Deshmukh, R. R., Singh, A. N., Martinez, M., Gandhi, N., Cotta, K. I., Parihar, H. S., & Mody, V. V. (2016) · Side effects of drugs annual · doi:10.1016/bs.seda.2016.08.026 · Cited by 3 · see citing works
Thyroid Hormones, Iodine and Iodides, and Antithyroid Drugs
Bhave, V., Patel, A., Deshmukh, R. R., Singh, A. N., & Mody, V. V. (2018) · Side effects of drugs annual · doi:10.1016/bs.seda.2018.08.011 · Cited by 3 · see citing works
(2015) · Elsevier eBooks · doi:10.1016/b978-0-444-53717-1.01406-2 · Cited by 3 · see citing works
Optimizing Levothyroxine Replacement in Primary Care Practice
Gunasekaran, K., & Tan, N. C. (2024) · IntechOpen eBooks · doi:10.5772/intechopen.1005906 · Cited by 2 · see citing works
Guay, D. R. P. (2018) · Springer eBooks · doi:10.1007/978-3-319-72416-4_3 · Cited by 2 · see citing works
Thyroid Hormones, Iodine and Iodides, and Antithyroid Drugs
Ethredge, H., Najafabadi, I. K., Deshmukh, R. R., Singh, A., & Mody, V. V. (2017) · Side effects of drugs annual · doi:10.1016/bs.seda.2017.06.017 · Cited by 1 · see citing works
ORGANIC ANION TRANSPORTING POLYPEPTIDES OATP
Tirona, R. G., & Kim, R. B. (2022) · Wiley eBooks · doi:10.1002/9781119739883.ch5 · Cited by 1 · see citing works
Self-citationAlternative Delivery Approaches for Levothyroxine (T4)
Anand, U., Agu, R. U., & Imran, S. A. (2013) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2013.08.074
Penatalaksanaan Pencabutan Gigi pada Pasien Hipertiroid
Arinawati, D. Y., Allam, A. S., & Aziz, R. Y. (2023) · STOMATOGNATIC - Jurnal Kedokteran Gigi · doi:10.19184/stoma.v20i2.44008
L’asse intestino-tiroide: come le alterazioni della barriera influenzano lo stato tiroideo
Restolfer, F., Pierro, P. D., Acampora, L., Sarnelli, G., & Dentice, M. (2025) · L Endocrinologo · doi:10.1007/s40619-025-01626-9
Selected case reports from the practice of a clinical pharmacist in the field of pneumology
Pelantová, B., Halvová, P., Rozsívalová, P., Dejdarová, L., Koblížek, V., Gabalec, F., & Malý, J. (2025) · Česká a slovenská farmacie · doi:10.36290/csf.2025.041
- Authors
- Goldberg, A. S., Tirona, R. G., Asher, L. J., Kim, R. B., & Van Uum, S. H. M.
- Affiliations
- Western University (CA)
- Division of Endocrinology and Metabolism, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Canada.
- Venue
- Thyroid
- Publisher
- SAGE Publications
- Published
- 2013-11
- Volume
- 23
- Issue
- 11
- Pages
- 1374-1378
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- OpenAlex
- W2091523885
- Cited by
- 25
- References
- 25
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 2 · 2016: 1 · 2015: 2 · 2013: 1
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Thyroid (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Lawson Health Research Institute
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- levothyroxine, ciprofloxacin, rifampicin, drug interactions, hypothyroidism, fluoroquinolones, rifamycin, intestinal absorption, thyroid hormone transporters
- MeSH terms
- Absorption, Administration, Oral, Adolescent, Adult, Ciprofloxacin, Double-Blind Method, Drug Interactions, Female, Humans, Hypothyroidism, Intestinal Absorption, Liver, Male, Prospective Studies, Rifampin, Thyroid Hormones, Thyroxine, Time Factors, Cross-Over Studies, Area Under Curve, Young Adult
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