Propranolol may slightly increase bioavailability of paracetamol, but this is unlikely to be clinically significant.
Clinical evidence,mechanism, importance and management
In a study in 10 healthy subjects, propranolol 80mg twice daily for 4 days increased half-life of a single 1.5-g dose of paracetamol by 25 % and lowered its clearance by 14%. The partial clearance of paracetamol to its cysteine and mercapturate derivatives was decreased by 16 % and 32%, respectively, and clearance to glucuronide conjugate was decreased by 27%, but sulfate was not significantly affected (See reference number 1). Similarly, an earlier study found that propranolol 40mg four times daily for one week increased maximum plasma level of a single 1.5-g dose of paracetamol and reduced time to peak plasma level. However, increased rate of absorption of paracetamol was not thought to be clinically important (See reference number 2). In contrast, a study in 6 subjects found that a relatively small dose of propranolol (80 mg daily for 6 days) did not affect pharmacokinetics of paracetamol (See reference number 3). Another study found that long-term propranolol use in patients with chronic liver disease did not influence clearance of total or unconjugated paracetamol (See reference number 4).
The changes described here appear to be small,and therefore unlikely to be clinically significant. Note that, it has been postulated, based on studies in animals, that propranolol may have a protective effect on paracetamol hepatic toxicity by inhibiting oxidative metabolism of paracetamol to toxic metabolites (See reference number 1,5).
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Sanchez-Martinez V,Tucker GT, Jackson PR, Lennard MS, Bax NDS, Woods HF. Lack of effect of propranolol on the kinetics of paracetamol in man. Br J Clin Pharmacol (1985) 20, 548P.
Hayes PC,Bouchier IAD. Effect of acute and chronic propranolol administration on antipyrineand paracetamol clearance in patients with chronic liver disease. Am J Gastroenterol (1989) 84, 723–6.
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