Effects of acetylsalicylic acid and paracetamol alone and in combination on prostanoid synthesis in man.

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Abstract
1 The present study was designed to investigate the effects of acetylsalicyclic 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 acetylsalicyclic acid or 3 g day-1 paracetamol or a combination of 1.5 g day-1 acetylsalicyclic 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.