THE EFFECT OF ACETAMINOPHEN ON PROSTACYCLIN PRODUCTION IN PREGNANT-WOMEN

OBJECTIVE: The purpose of this study was to determine if acetaminophen decreased prostacyclin production by endothelial cells in culture and by pregnant women. STUDY DESIGN: The effect of acetaminophen on endothelial cells in culture was determined by the addition of acetaminophen in concentrations of 1 0 and 1 00 mug/ml with comparison to control and indomethacin at 10 mug/ml. Prostacyclin production was estimated in 24 and thromboxane A2 production in six third-trimester pregnant women by measurement of excretion of urinary metabolites before and after ingestion of either 1000 mg of acetaminophen or placebo. RESULTS: Compared with control (549 +/- 61 pg/well, mean +/- SD), production of prostacyclin in vitro was significantly inhibited by acetaminophen at 1 0 mug/ml (321 +/- 25) and 1 00 mug/ml (257 +/- 14). This inhibition is similar to inhibition by 1 0 mug/ml of indomethacin (228 +/- 11). Excretion of prostacyclin metabolite was significantly lower after ingestion of acetaminophen (2233 +/- 446 vs 1246 +/- 199 pg/mg creatinine, mean +/- SEM) but unchanged after ingestion of placebo (1745 +/- 304 vs 1712 +/- 211). There was no difference in response between normal and hypertensive women, and there was no effect of acetaminophen on thromboxane metabolite excretion. CONCLUSION: Acetaminophen in typical oral doses results in reduced production of prostacyclin by endothelial cells in culture and in a reduction in prostacyclin, but not thromboxane, production in pregnant women.