The interaction of paracetamol with frusemide.
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).
Martin
U
U
University Department of Clinical Pharmacology, Royal Infirmary, Edinburgh.
Prescott
L F
LF
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000082:Acetaminophen / Q000494:pharmacology*; D000328:Adult; D015232:Dinoprostone / Q000652:urine; D004231:Diuresis / Q000187:drug effects*; D004347:Drug Interactions; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects*; D011863:Radioimmunoassay; D012083:Renin / Q000097:blood
D000082:Acetaminophen; D015121:6-Ketoprostaglandin F1 alpha; D005665:Furosemide; D012083:Renin; D015232:Dinoprostone