Limited usefulness of the breath test in evaluation of drug metabolism: a study in human oral contraceptive users treated with dimethylaminoantipyrine and diazepam

Abstract

Demethylation of 14C-dimethyl-N-aminoantipyrine (aminopyrine) and 14C-diazepam was measured by means of a breath test in women taking oral contraceptive steroids (OCS) and in controls not receiving OCS. Short-term half-life of 14CO2 in the breath after intake of 2 muCi of aminopyrine was significantly prolonged in women taking OCS when compared with controls. After intake of 2 muCi diazepam there were no statistically significant differences between the two groups. With 2 muCi diazepam or 10 muCi aminopyrine a biexponential decline of 14CO2 content in the breath was superimposed on a circadian, rhythm. 14CO2 in the aminopyrine breath test in the morning increased after the patients had risen from bed, whereas in the diazepam breath test the 14CO2 content decreased. It is concluded that the effect of OCS on drug metabolism is very specific. Furthermore, the appearance of 14CO2 in the breath does not depend only on hepatic microsomal demethylation.

PIP: 30 healthy female volunteers were tested in 5 groups of 6 persons each to evaluate whether oral contraceptives (OCs) had inhibiting effects on the disposal, via the hepatic microsomal enzyme system, of radiolabeled diazepam. Therefore, demethylation of radiolabeled aminopyrine and diazepam was measured by a breath test in women using OCs and in controls. Short-term half-life of radiolabeled carbon dioxide in the breath after ingestion of 2 mcCi of aminopyrine was significantly prolonged in women using OCs compared with controls. After ingestion of 2 mcCi of diazepan there was no statistically significant difference between the 2 groups. With 2 mcC; of diazepam or 10 mcCi of aminopyrine, a biexponential decline of radiolabeled carbon dioxide content in the breath was superimposed on a circadian rhythm, and the carbon dioxide in the aminopyrine breath test increased after patients had risen from bed whereas it decreased in the diazepam test. It is concluded that the effect of OCs on drug metabolism is very specific, and that furthermore, the appearance of radiolabeled carbon dioxide in the breath does not depend only on hepatic microsomal demethylation.