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  • Title: Increased metabolic clearance of acetaminophen with oral contraceptive use.
    Author: Abernethy DR, Divoll M, Ochs HR, Ameer B, Greenblatt DJ.
    Journal: Obstet Gynecol; 1982 Sep; 60(3):338-41. PubMed ID: 6897933.
    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.
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