Impairment of antipyrine metabolism by low-dose oral contraceptive steroids

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Abstract
The effect of low-dose oral contraceptive steroids (OCS) on the kinetics of i.v. antipyrine was determined. Eight women (age, 23.1 .+-. 1.1 yr (.hivin.x .+-. SE); wt, 57.8 .+-. 2.2 kg) using low-dose (.gtoreq. 50 .mu.g) estrogen oral contraceptive steroids (OCS) on a long-term basis were age- and wt-matched with 8 controls (age, 23.4 .+-. 0.8 yr; wt, 58.4 .+-. 2.1 kg) not using OCS. All were nonsmokers taking no other drugs. OCS subjects had a longer antipyrine elimination half-life (t1/2.beta.) than the controls (17.3 .+-. 1.6 and 10.5 .+-. 0.8 h; P < 0.005). Volume of distribution was similar for both groups (0.59 .+-. 0.02 l/kg [OCS] and 0.58 .+-. 0.02 l/kg). Total metabolic clearance of antipyrine was slowed in OCS subjects (0.41 .+-. 0.03 and 0.66 .+-. 0.05 ml/min per kg; P < 0.001). Since volume of distribution and body wt are of the same order in both groups, prolongation of antipyrine t1/2.beta. is the result of decreased total metabolic clearance. Even low-dose estrogen containing OCS may impair clearance of other drugs.