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Br J Clin Pharmacol. 1987 Jun;23(6):721-5.

Paracetamol interaction with oral contraceptive steroids: increased plasma concentrations of ethinyloestradiol.


The effect of a single dose of paracetamol (1 g) on plasma concentrations of the oral contraceptive steroids ethinyloestradiol (EE2) and levonorgestrel (LNG) has been studied in six healthy female volunteers. The area under the plasma concentration-time curve (AUC0-24) of EE2 was significantly increased following paracetamol administration by 22% (control 2221 +/- 291; following paracetamol, 2702 +/- 452 pg ml-1 h; mean +/- s.d.; P less than or equal to 0.05). The greatest effect was evident in the time period 0-3 h. There was a significant decrease in the AUC of EE2-sulphate after paracetamol (7736 +/- 3791 pg ml-1 h) compared with control (13161 +/- 4535 pg ml-1 h; P less than or equal to 0.05). Plasma concentrations of LNG were unaltered by concurrent paracetamol administration. We conclude that the administration of a single 1 g dose of paracetamol causes an increase in plasma concentrations of EE2 as a result of a reduction in the sulphation of the steroid. This interaction may be of clinical significance in women on oral contraceptive steroids who regularly take paracetamol.


The availability of the oral contraceptive steroids ethinyl estradiol (EE) and levonorgestrel in plasma after a single dose of 1 g paracetamol (acetaminophen) was quantitated. 6 women aged 21-24 who had been taking combined oral contraceptives for at least 3 months took a single dose of 1 g paracetamol, followed 1 hour later by a single dose of Ovran (50 mcg EE and 250 mch levonorgestrel) after an overnight fast. EE and levonorgestrel were radioimmunoassayed, and EE sulfate was determined by radioimmunoassay after incubation with sulfatase. In blood sampled over a 24 hour period, the area under the concentration curve for EE during the 1st 3 hours rose significantly after paracetamol (22%, p0.05). EE sulfate concentration was significantly lower (p0.05). There was no change in plasma concentration of levonorgestrel. The results suggest that paracetamol increases circulating EE by limiting available sulfation of the steroid.

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