The effect of antipyrine, phenobarbitol and rifampicin on thyroid hormone metabolism in man
Abstract
Abstract. The effect of three different liver microsomal enzyme inducing drugs on thyroid hormone metabolism was investigated. Seven volunteers were randomly allocated in a crossover design to either antipyrine (1200 mg), phenobarbital (100 mg) or rifampicin (1200 mg) daily for 14 days. Before and after each treatment the following parameters of enzyme induction were measured: antipyrine clearance, y‐glutamyltranspepti‐dase, d‐glucaric acid and 6‐β‐hydroxycortisol urinary excretion. In addition, thyroxine‐binding globulin (TBG), T 3‐resin uptake (RT 3 U), thyroxine (T 4), free thyroxine (FT 4), triiodothyronine (T 3), reverse T 3 (rT 3), and thyroid stimulating hormone (TSH) were estimated. Following antipyrine and phenobarbital antipyrine clearance increased by about 45%, while with rifampicin an increase of 125% was observed. The indices of thyroid function did not change following phenobarbital and antipyrine, but after rifampicin T 4, FT 4 and rT 3 decreased by about 14%, and T 3 increased by 25%. In addition, the impact of rifampicin on the clearance of injected 125 I‐T 4 was investigated in six additional volunteers by blocking thyroid iodine uptake. The 125 I‐T 4 halflife decreased from 155 to 106 h and its clearance increased from 35 to 50 ml/h, while a fall in T 4, FT 4 and rT 3 by about 40% and no rise but a decrease in T 3 by 25% occurred. Therefore an increased clearance of T 4 and rT 3 but not of T 3 seems likely following rifampicin, which might be due to enhanced hepatic metabolism and biliary excretion.
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The effect of phenobarbital to increase T4 and T3 metabolism has been documented in rodents and humans, but effects on thyroid function are more notable in rats.
“The effect of phenobarbital to increase T 4 and T3 metabolism has been documented in rodents (173) and humans (174,175), but effects on thyroid function are more notable in rats (172).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [175]
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- Authors
- OHNHAUS, E. E., BÜRGI, H., BURGER, A., & STUDER, H.
- Affiliations
- University of Bern (CH)
- Corresponding author
- OHNHAUS, E. E.
- ORCID
- Venue
- European Journal of Clinical Investigation
- Publisher
- Wiley
- Published
- 1981-10
- Volume
- 11
- Issue
- 5
- Pages
- 381-387
- ISSN
- 0014-2972 (ISSN-L)
- 1365-2362
- OpenAlex
- W2032097425
- Cited by
- 50
- References
- 54
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2020: 2 · 2019: 1 · 2018: 1 · 2015: 1 · 2014: 1 · 2013: 2 · 2012: 1
- FWCI
- 0.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Clinical Investigation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- antipyrine, phenobarbital, rifampicin, microsomal enzyme induction, thyroid hormone metabolism, reverse T3, free thyroxine, triiodothyronine, thyroid-stimulating hormone, thyroxine-binding globulin, antipyrine clearance, gamma-glutamyltranspeptidase, glucaric acid, hepatic metabolism, biliary excretion, thyroid function
- MeSH terms
- Adult, Antipyrine, Enzyme Induction, Female, Humans, Male, Microsomes, Liver, Phenobarbital, Rifampin, Thyroid Hormones, Thyrotropin, Thyroxine
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