Influence of mild thyroid dysfunction on antipyrine clearance and metabolite formation in man

The salivary kinetics and rates of metabolite formation of antipyrine were studied in 6 hyperthyroid and 6 hypothyroid out-patients on 2 occasions, on admission and when T3 and T4 levels had returned to normal after treatment with carbimazole (hyperthyroidism) or l-thyroxine (hyperthyroidism). In hyperthyroidism the half-life of antipyrine was significantly shorter (p less than 0.05) than after recovery (9.3 +/- 1.0 versus 10.6 +/- 0.9 h). Hypothyroid patients showed a significantly longer elimination half-life before treatment than after recovery (12.7 +/- 2.6 versus 10.3 +/- 2.6 h). Antipyrine clearance in hyperthyroid patients was decreased after treatment from 2.7 +/- 0.3 to 2.4 +/- 0.3 l/h, and it was increased in hypothyroid patients from 2.1 +/- 0.4 to 2.5 +/- 0.5 l/h (p less than 0.05). The changes in clearances for the production of the antipyrine metabolites 4-hydroxyantipyrine (OHA), norantipyrine (NORA) and 3-hydroxymethylantipyrine (HMA) were of the same order of magnitude as total antipyrine clearance, and no selectivity towards any of the metabolic pathways of antipyrine was apparent. Mild thyroid dysfunction seems to affect oxidative drug metabolizing enzyme activity in a non-selective manner and only to a small extent (10-30%). It is suggested that adjustment of the therapeutic regimens of various drugs in mild thyroid disease will only rarely by required on the basis of pharmacokinetic considerations.