The effect of antipyrine, phenobarbitol and rifampicin on thyroid hormone metabolism in man

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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), T3‐resin uptake (RT3U), thyroxine (T4), free thyroxine (FT4), triiodothyronine (T3), reverse T3 (rT3), 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 T4, FT4 and rT3 decreased by about 14%, and T3 increased by 25%.In addition, the impact of rifampicin on the clearance of injected 125I‐T4 was investigated in six additional volunteers by blocking thyroid iodine uptake. The 125I‐T4 halflife decreased from 155 to 106 h and its clearance increased from 35 to 50 ml/h, while a fall in T4, FT4 and rT3 by about 40% and no rise but a decrease in T3by 25% occurred. Therefore an increased clearance of T4 and rT3 but not of T3 seems likely following rifampicin, which might be due to enhanced hepatic metabolism and biliary excretion.