The interaction of paracetamol with frusemide.

Abstract

Following the administration of paracetamol (1 g 4 times per day) or placebo to 10 healthy female volunteers for 2 days, the pharmacological effects of intravenous frusemide (20 mg) were observed after a final dose of either paracetamol or placebo. Paracetamol pre‐treatment had no effect on frusemide‐induced diuresis or natriuresis. There was a significant reduction in the basal output of prostaglandin E2 (PGE2) with paracetamol pre‐treatment (18.4 +/‐ 15.4 vs 7.6 +/‐ 5.0 ng h‐1, P < 0.05; 95% confidence interval of the difference 0.2 to 21.8). Frusemide induced a transient increase in the urinary excretion rate of PGE2 and although this effect was reduced by paracetamol (46.6 +/‐ 50.9 vs 23.2 +/‐ 13.8) the differences in the change of excretion rate from baseline were not statistically significant (95% confidence interval of the difference ‐17.8 to 15.7). The basal level of 6‐keto prostaglandin F1 alpha (PGF1 alpha) was less with paracetamol pre‐treatment (61.7 +/‐ 41.1 vs 38.7 +/‐ 26.1 ng h‐1, NS; 95% confidence interval of the difference ‐16.6 to 62.6) and the cumulative urinary output of PGF1 alpha in the 6 h after frusemide administration was significantly reduced (305.9 +/‐ 179.4 vs 181.8 +/‐ 100.2 ng h‐1, P < 0.05; 95% confidence interval of the difference 32.2 to 216). The frusemide‐ induced rise in plasma renin activity was significantly less with paracetamol than placebo at 60 min (4.3 +/‐ 2.9 vs 2.7 +/‐ 1.9 ng ml‐1 h‐1, P < 0.01; 95% confidence interval of the difference 0.4 to 2.7). 1994 The British Pharmacological Society