The effect of propranolol on paracetamol metabolism in man

Ten healthy volunteers were treated for 4 days with 160 mg propranolol HCl and placebo in random order. At the end of each treatment salivary antipyrine kinetics and the plasma kinetics and urinary excretion of paracetamol and its major metabolites were measured following a 1500 mg oral dose. Propranolol prolonged the half-life of antipyrine by 11 +/- 5% (mean +/- s.e. mean) and lowered its clearance by 14 +/- 3% (P less than 0.05). Propranolol increased the half-life of paracetamol by 25 +/- 12% (P less than 0.05) and lowered its clearance by 14 +/- 3% (P less than 0.05). Propranolol decreased the partial clearance of paracetamol to its cysteine and mercapturate derivatives by 16 +/- 3% (P less than 0.05) and 32 +/- 7% (P less than 0.05), respectively. The partial clearance to the glucuronide conjugate was decreased by 27 +/- 6% (P less than 0.05), whereas that to sulphate was not changed significantly. Propranolol inhibits paracetamol metabolism predominantly through inhibition of the oxidation and glucuronidation pathways.