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 < 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 Fia, 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 < 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 halflife. 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.
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