Increased metabolic clearance of acetaminophen with oral contraceptive use

Obstet Gynecol. 1982 Sep;60(3):338-41.

Abstract

The effect of chronic low-dose oral contraceptive steroid use on the pharmacokinetics of intravenous acetaminophen was determined. Eight women using low-dose (under 50 micrograms) estrogen oral contraceptive steroid for more than 3 months were matched for age and weight (mean age, 25.9 years; mean weight, 58.3 kg) with 8 female controls not using the steroid (mean age, 26.0 years; mean weight, 55.5 kg). No subject was taking other drugs. Oral contraceptive steroid subjects had a lower elimination half-life of acetaminophen (2.12 hours) than controls (2.71 hours) (P less than .005). Volume of distribution was similar for both groups (oral contraceptive group, 1.04 liters/kg; controls, 0.96 liters/kg; NS). Total metabolic clearance was significantly higher in oral contraceptive subjects (5.81 ml/min/kg, versus 4.12 ml/min/kg for controls; P less than .02). As volume of distribution and body weight are similar for both groups, the decrease in acetaminophen elimination half-life among contraceptive steroid users is the result of increased total metabolic clearance. Thus, low-dose estrogen oral contraceptive steroid may stimulate the metabolism of a conjugatively metabolized drug such as acetaminophen, in contrast to contraceptive steroid impairment of the clearance of some oxidatively metabolized drugs, with antipyrine being the prototype.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetaminophen / metabolism*
  • Adult
  • Body Weight
  • Contraceptives, Oral / pharmacology*
  • Contraceptives, Oral, Hormonal / pharmacology*
  • Drug Interactions
  • Estrogens / pharmacology*
  • Female
  • Half-Life
  • Humans
  • Kinetics
  • Metabolic Clearance Rate
  • Time Factors

Substances

  • Contraceptives, Oral
  • Contraceptives, Oral, Hormonal
  • Estrogens
  • Acetaminophen