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 10 and 100 Wg/ml with comparison to control and indomethacin at 10 Wg/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 10 Wg/ml (321 ± 25) and 100 lLg/ml (257 ± 14). This inhibition is similar to inhibition by 10 lLg/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.