Impairment of antipyrine metabolism by low-dose oral contraceptive steroids

Abstract

The effect of low-dose oral contraceptive steroids (OCS) on the kinetics of intravenous antipyrine was determined. Eight women (age, 23.1 +/- 1.1 yr (mean +/- SE); weight, 57.8 +/- 2.2 kg) using low-dose (less than or equal to 50 micrograms) estrogen oral contraceptive steroids (OCS) on a long-term basis were age- and weight-matched with eight controls (age, 23.4 +/- 0.8 yr; weight, 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 hr; p less than 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/kg; p less than 0.001). Since volume of distribution and body weight are of the same order in both groups, prolongation of antipyrine t1/2 beta is the result of decreased total metabolic clearance. Thus, even low-dose estrogen containing OCS may impair clearance of other drugs.

PIP: The effects of low-dose oral contraceptives (Ortho-Novum 1/50, Norinyl 1/50, Zorane 1.5/30, Lo/Ovral, and Modicon) on the kinetics of intravenous antipyrine were studied because of its indications of liver microsomal enzyme alterations. 8 healthy nonsmoking women aged 20-26 years, taking the pills for more than 3 months, were studied. They were compared with 8 matched noncontraceptive using controls. Kinetic variables were similar in the case and control groups; these variables incluced initial distribution, half-life, apparent central compartment volume, and total apparent volume of distribution. However, mean clearance was much lower in the cases (.41 and .66 ml per minute per kgm; P.001). This difference in clearance resulted in prologation of the elimination half-life (17.3 and 10.5 hours; P.005) in users. Since volume of distribution and body weight were on the same order in both groups, prologation of antipyrine elimination half-life must result from decreased total metabolic clearance, implying that even low-dose estrogen-containing oral contraceptives may impair clearance of other drugs.