The comparative effects of paracetamol and indomethacin on renal function in healthy female volunteers.

Abstract

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.

Characterization of Organic Anion Transporter 2 (SLC22A7): A Highly Efficient Transporter for Creatinine and Species-Dependent Renal Tubular Expression

“…However, IMC is a potent prostaglandin synthesis inhibitor, and the mechanisms other than transporter inhibition have been implicated in its inhibitory effects. In addition, although there are reports that IMC had no effect on creatinine renal clearance in humans (Levey et al, 1988;Prescott et al, 1990), the unchanged clearance could be confounded by consumption of a high-protein meal (Levey et al, 1988). Information about the inhibition of creatinine clearance by BSP in humans is lacking, because BSP is a contrast agent used as a diagnostic aid in liver function test.…”

Determinants and sequelae associated with utilization of acetaminophen versus traditional nonsteroidal antiinflammatory drugs in an elderly population

“…Acetaminophen at daily doses of Ͼ500 mg has been shown to inhibit prostacyclin synthesis in humans, which may diminish gastric mucosal protection (13), and to affect kidneys, neural tissue, and platelets (37)(38)(39)(40)(41). Results of a recent study by Catella-Lawson et al showed that acetaminophen at high doses is a weak, reversible, isoform-nonspecific COX inhibitor and suggested that 3052 RAHME ET AL acetaminophen may have GI side effects (16).…”

The Complexities of Interpreting Reversible Elevated Serum Creatinine Levels in Drug Development: Does a Correlation with Inhibition of Renal Transporters Exist?

“…Indomethacin is a relatively potent in vitro inhibitor of OAT2 (IC 50 = 2.1 mM) (Shen et al, 2015). However, the effect of indomethacin on elevation of SCr in several clinical studies is controversial (Prescott et al, 1990;Al-Waili, 2002). In female healthy volunteers, indomethacin (150 mg daily for 3 days) had no significant effect on SCr, GFR, or renal blood flow (Prescott et al, 1990).…”

“…However, the effect of indomethacin on elevation of SCr in several clinical studies is controversial (Prescott et al, 1990;Al-Waili, 2002). In female healthy volunteers, indomethacin (150 mg daily for 3 days) had no significant effect on SCr, GFR, or renal blood flow (Prescott et al, 1990). However, indomethacin was reported to increase SCr in neonates (AlWaili, 2002).…”