THE COMPARATIVE EFFECTS OF PARACETAMOL AND INDOMETHACIN ON RENAL-FUNCTION IN HEALTHY FEMALE VOLUNTEERS

1. Renal function was assessed in 10 healthy female volunteers during administration of placebo, paracetamol (acetaminophen) (4.0 g daily) and indomethacin (150 mg daily) for 3 days under conditions of controlled sodium and fluid intake. 2. Paracetamol and indomethacin had no significant effect on the glomerular filtration rate and effective renal plasma flow as measured by the renal clearances of inulin, creatinine and p‐aminohippurate (PAH). 3. Compared with placebo, paracetamol reduced the mean urinary excretion of prostaglandin E2 by 43% on the second day and 58% on the third treatment day (P less than 0.01). With indomethacin the corresponding reductions were 73 and 80%. Paracetamol and indomethacin had much less effect on the excretion of prostaglandin 6‐keto F1 alpha, and a significant decrease was observed only on the third day. 4. The decreased urinary excretion of prostaglandin E2, produced by paracetamol was associated with a reduction in sodium excretion of more than 50% (P less than 0.01) and delay in the onset of diuresis following an acute water load. 5. The renal effects of paracetamol and indomethacin appear to differ. Although indomethacin reduced prostaglandin excretion more than paracetamol it had a similar effect on sodium excretion and less initial antidiuretic action. Unlike paracetamol, indomethacin also reduced basal plasma renin activity. 6. Paracetamol reduced the total body clearance of PAH and increased its plasma half‐life. This effect could be attributed to inhibition of the acetylation of PAH by paracetamol. 7. In normal use paracetamol does not appear to have the adverse renal effects associated with the non‐steroidal anti‐ inflammatory analgesics and further studies are required to establish the clinical significance of these findings. 1990 The British Pharmacological Society