EFFECTS OF ACETYLSALICYLIC-ACID AND PARACETAMOL ALONE AND IN COMBINATION ON PROSTANOID SYNTHESIS IN MAN

1. The present study was designed to investigate the effects of acetylsalicylic acid and paracetamol given separately and in combination on total body and renal PGE2 synthesis in healthy volunteers. 2. In a randomized four‐way cross‐over study eleven female volunteers received for two consecutive days 3 g day‐1 acetylsalicylic acid or 3 g day‐1 paracetamol or a combination of 1.5 g day‐1 acetylsalicylic acid and 1.5 g day‐1 paracetamol, or 1.5 g day‐1 acetylsalicylic acid separated by washout phases of at least 5 days. Urinary excretion of the major urinary metabolite of PGE2 (PGE‐MUM), PGE2 and creatinine clearance were measured before and on day 2 of each treatment period. Compliance was tested by measuring metabolites of the two drugs in urine. 3. Paracetamol did not reduce urinary excretion of PGE2 whereas both dosages of acetylsalicylic acid caused a significant reduction. 4. The combination of both drugs did not reduce PGE2 excretion more than acetylsalicylic acid alone. 5. All four drug schedules reduced urinary excretion of PGE‐MUM significantly. 1990 The British Pharmacological Society