Inhibition of hepatic demethylation of aminopyrine by oral contraceptive steroids in humans.

The effect of oral contraceptive steroids (OCS) on the rate of hepatic demethylation of 14C-dimethylaminoantipyrine (DAP) was studied directly in healthy young volunteers using a newly developed noninvasive breath analysis technique. After oral administration of a trace dose of DAP the specific activity of 14CO2 in breath was determined during 6 h and expressed as half life. The half life of eighteen female and twelve male control subjects was 2.4 +/- 1.2 h (2 SD) and 2.2 +/- 0.6 h (2 SD), respectively. In seven women starting OCS a progressive prolongation of DAP half life during a single menstrual period was observed. In seventeen women who had taken OCS in 21 day cycles, for more than 3 months, the half life was significantly (P less than 0.001) prolonged (4.4 +/- 2.1 h) when measured after 21 consecutive days of OCS intake. On average, stopping OCS for 7 days or giving phenobarbital in addition to OCS shortened DAP half life significantly (from 4.4 +/- 2.1 h to 3.2 +/- 1.1 h, n = 17, P less than 0.005; and from 4.6 +/- 2.0 h to 3.2 +/- 1.0 h, n = 12, P less than 0.01, respectively). Eight of twelve women on OCS responded to OCS intake and to OCS cessation and phenobarbital, whereas four women did not respond to any of these measures. These data suggest that inhibition of hepatic demethylation of DAP by OCS is time dependent and reversible. The extent of inhibition appears to be an individual characteristic of a given person.