ACUTE EFFECTS OF PARACETAMOL ON PROSTAGLANDIN SYNTHESIS AND RENAL-FUNCTION IN NORMAL MAN AND IN PATIENTS WITH RENAL-FAILURE

The effects of oral dosing with paracetamol (40 mg/kg/day for 3 days) on serum thromboxane B2 (TXB2), glomerular filtration rate (GFR), sodium homeostasis, urinary excretion of prostaglandin E2 (PGE2) and on some other renal function parameters were investigated in 10 healthy young controls aged 23-26 years, 9 healthy elderly persons with normal renal function aged 66-78 years and 9 patients with chronic stable impaired renal function. Plasma paracetamol concentration was unaffected by age and GFR, whereas the sulphate and glucuronide metabolites of paracetamol accumulated substantially in patients with renal failure, and to a lesser degree in elderly controls. Serum TXB2 was significantly reduced 1 and 4 hours after oral ingestion of a single dose of paracetamol (18 mg/kg), but the values were normalized after 12 hours. Urinary sodium excretion was reduced by 23.4% on the first treatment day in elderly controls, but unchanged in young controls and in patients with renal failure. Urinary excretion of PGE2 was unchanged in young controls, but reduced by 35.9% on the first day on paracetamol treatment in elderly controls and from 22-29% on the 3 days on paracetamol in patients with impaired renal function. Paracetamol was without effect on potassium homeostasis or on the excretion of glandular kallikrein or proteins in urine. Our study indicates that oral treatment with paracetamol in therapeutic doses reversibly reduces serum TXB2 for at least 4 hours after ingestion both in healthy controls and in patients with impaired renal function. Our data also suggest that paracetamol effects renal PGE2 excretion, especially in patients with impaired renal function. Renal glomerular and tubular function parameters were unchanged by paracetamol.