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. 1990 Feb;29(2):261–264. doi: 10.1111/j.1365-2125.1990.tb03631.x

The effect of propranolol on paracetamol metabolism in man.

O Z Baraka 1, C A Truman 1, J M Ford 1, C J Roberts 1
PMCID: PMC1380095  PMID: 2306420

Abstract

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adriaenssens P. I., Prescott L. F. High performance liquid chromatographic estimation of paracetamol metabolites in plasma. Br J Clin Pharmacol. 1978 Jul;6(1):87–88. doi: 10.1111/j.1365-2125.1978.tb01687.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bax N. D., Lennard M. S., Tucker G. T. Inhibition of antipyrine metabolism by beta-adrenoceptor antagonists. Br J Clin Pharmacol. 1981 Dec;12(6):779–784. doi: 10.1111/j.1365-2125.1981.tb01306.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Corcoran G. B., Mitchell J. R., Vaishnav Y. N., Horning E. C. Evidence that acetaminophen and N-hydroxyacetaminophen form a common arylating intermediate, N-acetyl-p-benzoquinoneimine. Mol Pharmacol. 1980 Nov;18(3):536–542. [PubMed] [Google Scholar]
  4. Danhof M., Groot-van der Vis E., Breiner D. D. Assay of antipyrine and its primary metabolites in plasma, saliva and urine by high-performance liquid chromatography and some preliminary results in man. Pharmacology. 1979;18(4):210–223. doi: 10.1159/000137254. [DOI] [PubMed] [Google Scholar]
  5. Deacon C. S., Lennard M. S., Bax N. D., Woods H. F., Tucker G. T. Inhibition of oxidative drug metabolism by beta-adrenoceptor antagonists in related to their lipid solubility. Br J Clin Pharmacol. 1981 Sep;12(3):429–431. doi: 10.1111/j.1365-2125.1981.tb01240.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Greenblatt D. J., Franke K., Huffman D. H. Impairment of antipyrine clearance in humans by propranolol. Circulation. 1978 Jun;57(6):1161–1164. doi: 10.1161/01.cir.57.6.1161. [DOI] [PubMed] [Google Scholar]
  7. Hawksworth G., Betts T., Crowe A., Knight R., Nyemitei-Addo I., Parry K., Petrie J. C., Raffle A., Parsons A. Diazepam/beta-adrenoceptor antagonist interactions. Br J Clin Pharmacol. 1984;17 (Suppl 1):69S–76S. doi: 10.1111/j.1365-2125.1984.tb02431.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Meredith T. J., Goulding R. Paracetamol. Postgrad Med J. 1980 Jul;56(657):459–473. doi: 10.1136/pgmj.56.657.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Miners J. O., Wing L. M., Lillywhite K. J., Robson R. A. Selectivity and dose-dependency of the inhibitory effect of propranolol on theophylline metabolism in man. Br J Clin Pharmacol. 1985 Sep;20(3):219–223. doi: 10.1111/j.1365-2125.1985.tb05064.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Miners J. O., Wing L. M., Lillywhite K. J., Smith K. J. Failure of 'therapeutic' doses of beta-adrenoceptor antagonists to alter the disposition of tolbutamide and lignocaine. Br J Clin Pharmacol. 1984 Dec;18(6):853–860. doi: 10.1111/j.1365-2125.1984.tb02555.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mitchell M. C., Hanew T., Meredith C. G., Schenker S. Effects of oral contraceptive steroids on acetaminophen metabolism and elimination. Clin Pharmacol Ther. 1983 Jul;34(1):48–53. doi: 10.1038/clpt.1983.127. [DOI] [PubMed] [Google Scholar]
  12. Mitchell M. C., Schenker S., Speeg K. V., Jr Selective inhibition of acetaminophen oxidation and toxicity by cimetidine and other histamine H2-receptor antagonists in vivo and in vitro in the rat and in man. J Clin Invest. 1984 Feb;73(2):383–391. doi: 10.1172/JCI111223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ochs H. R., Carstens G., Greenblatt D. J. Reduction in lidocaine clearance during continuous infusion and by coadministration of propranolol. N Engl J Med. 1980 Aug 14;303(7):373–377. doi: 10.1056/NEJM198008143030705. [DOI] [PubMed] [Google Scholar]
  14. Ochs H. R., Greenblatt D. J., Verburg-Ochs B. Propranolol interactions with diazepam, lorazepam, and alprazolam. Clin Pharmacol Ther. 1984 Oct;36(4):451–455. doi: 10.1038/clpt.1984.203. [DOI] [PubMed] [Google Scholar]
  15. Peet M., Middlemiss D. N., Yates R. A. Pharmacokinetic interaction between propranolol and chlorpromazine in schizophrenic patients. Lancet. 1980 Nov 1;2(8201):978–978. doi: 10.1016/s0140-6736(80)92135-2. [DOI] [PubMed] [Google Scholar]
  16. Perucca E., Richens A. Paracetamol disposition in normal subjects and in patients treated with antiepileptic drugs. Br J Clin Pharmacol. 1979 Feb;7(2):201–206. doi: 10.1111/j.1365-2125.1979.tb00922.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Prescott L. F., Critchley J. A., Balali-Mood M., Pentland B. Effects of microsomal enzyme induction on paracetamol metabolism in man. Br J Clin Pharmacol. 1981 Aug;12(2):149–153. doi: 10.1111/j.1365-2125.1981.tb01193.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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