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.


METHODS
The effect of acetaminophen on endothelial cells in culture was determined by the addition of acetaminophen in concentrations of 10 and 100 micrograms/ml with comparison to control and indomethacin at 10 micrograms/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 micrograms/ml (321 +/- 25) and 100 micrograms/ml (257 +/- 14). This inhibition is similar to inhibition by 10 micrograms/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.


CONCLUSIONS
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.
O'Brien
W F
WF
Department of Obstetrics and Gynecology, University of South Florida College of Medicine, Tampa 33606.
Krammer
J
J
O'Leary
T D
TD
Mastrogiannis
D S
DS
D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives / Q000652:urine; D000082:Acetaminophen / Q000494:pharmacology*; D000328:Adult; D002478:Cells, Cultured; D004311:Double-Blind Method; D004727:Endothelium / Q000166:cytology; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D011247:Pregnancy / Q000378:metabolism*; D011249:Pregnancy Complications, Cardiovascular / Q000378:metabolism; D011263:Pregnancy Trimester, Third / Q000378:metabolism; D013928:Thromboxane A2 / Q000096:biosynthesis
D000082:Acetaminophen; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; D011464:Epoprostenol; D007213:Indomethacin