Skip to main content
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1979 Jan;7(1):49–54. doi: 10.1111/j.1365-2125.1979.tb00896.x

The effect of ageing on the hepatic clearance of propranolol.

C M Castleden, C F George
PMCID: PMC1429596  PMID: 760742

Abstract

1. Plasma propranolol concentrations were measured in healthy old and young subjects following single oral doses of 40 mg, single i.v. infusions of 0.15 mg kg-1 and after nine 40 mg oral doses given four times daily. 2. In each of the three studies, the elderly had higher plasma propranolol concentrations than the young despite having similar apparent volumes of distribution. 3. The terminal half-life of propranolol was similar in the two groups after oral propranolol but significantly shorter in the young after intravenous dosing (P less than 0.05). 4. The bioavailability assessed from the concentration-time curves after i.v. and oral dosing was greater in the elderly (P less than 0.05). 5. The differences between peak concentrations observed in old and young subjects after single oral doses were maintained during chronic therapy and there was a correlation between the individual values obtained on multiple therapy with that after a single dose (P less than 0.05). 6. Ageing appears to affect the pharmacokinetics of propranolol in two ways. Firstly, distribution to the tissues appears to be slowed. Secondly, the increased bioavailability following oral administration suggests diminished intrinsic clearance by metabolism.

Full text

PDF

Selected References

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

  1. BENDER A. D. THE EFFECT OF INCREASING AGE ON THE DISTRIBUTION OF PERIPHERAL BLOOD FLOW IN MAN. J Am Geriatr Soc. 1965 Mar;13:192–198. doi: 10.1111/j.1532-5415.1965.tb02665.x. [DOI] [PubMed] [Google Scholar]
  2. BRANDFONBRENER M., LANDOWNE M., SHOCK N. W. Changes in cardiac output with age. Circulation. 1955 Oct;12(4):557–566. doi: 10.1161/01.cir.12.4.557. [DOI] [PubMed] [Google Scholar]
  3. Branch R. A., Nies A. S., Shand D. G. The disposition of propranolol. 8. General implications of the effects of liver blood flow on elimination from the perfused rat liver. Drug Metab Dispos. 1973 Sep-Oct;1(5):687–690. [PubMed] [Google Scholar]
  4. Coltart D. J., Shand D. G. Plasma propranolol levels in the quaniitative assessment of beta-adrenergic blockade in man. Br Med J. 1970 Sep 26;3(5725):731–734. doi: 10.1136/bmj.3.5725.731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Conney A. H. Pharmacological implications of microsomal enzyme induction. Pharmacol Rev. 1967 Sep;19(3):317–366. [PubMed] [Google Scholar]
  6. Evans G. H., Nies A. S., Shand D. G. The disposition of propranolol. 3. Decreased half-life and volume of distribution as a result of plasma binding in man, monkey, dog and rat. J Pharmacol Exp Ther. 1973 Jul;186(1):114–122. [PubMed] [Google Scholar]
  7. Evans G. H., Shand D. G. Disposition of propranolol. V. Drug accumulation and steady-state concentrations during chronic oral administration in man. Clin Pharmacol Ther. 1973 Jul-Aug;14(4):487–493. doi: 10.1002/cpt1973144part1487. [DOI] [PubMed] [Google Scholar]
  8. George C. F., Orme M. L., Buranapong P., Macerlean D., Breckenridge A. M., Dollery C. T. Contribution of the liver to overall elimination of propranolol. J Pharmacokinet Biopharm. 1976 Feb;4(1):17–27. doi: 10.1007/BF01271441. [DOI] [PubMed] [Google Scholar]
  9. Greenblatt D. J., Koch-Weser J. Adverse reactions to propranolol in hospitalized medical patients: a report from the Boston Collaborative Drug Surveillance Program. Am Heart J. 1973 Oct;86(4):478–484. doi: 10.1016/0002-8703(73)90139-7. [DOI] [PubMed] [Google Scholar]
  10. Harris P. A., Riegelman S. Influence of the route of administration on the area under the plasma concentration-time curve. J Pharm Sci. 1969 Jan;58(1):71–75. doi: 10.1002/jps.2600580114. [DOI] [PubMed] [Google Scholar]
  11. Hayes M. J., Langman M. J., Short A. H. Changes in drug metabolism with increasing age: 1. warfarin binding and plasma proteins. Br J Clin Pharmacol. 1975 Feb;2(1):69–72. doi: 10.1111/j.1365-2125.1975.tb00474.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hayes M. J., Langman M. J., Short A. H. Changes in drug metabolism with increasing age: 2. phenytoin clearance and protein binding. Br J Clin Pharmacol. 1975 Feb;2(1):73–79. doi: 10.1111/j.1365-2125.1975.tb00475.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kato R., Takanaka A. Effect of phenobarbital on electron transport system, oxidation and reduction of drugs in liver microsomes of rats of different age. J Biochem. 1968 Mar;63(3):406–408. [PubMed] [Google Scholar]
  14. McDevitt D. G., Frisk-Holmberg M., Hollifield J. W., Shand D. G. Plasma binding and the affinity of propranolol for a beta receptor in man. Clin Pharmacol Ther. 1976 Aug;20(2):152–157. doi: 10.1002/cpt1976202152. [DOI] [PubMed] [Google Scholar]
  15. Nies A. S., Evans G. H., Shand D. G. The hemodynamic effects of beta adrenergic blockade on the flow-dependent hepatic clearance of propranolol. J Pharmacol Exp Ther. 1973 Mar;184(3):716–720. [PubMed] [Google Scholar]
  16. O'Malley K., Crooks J., Duke E., Stevenson I. H. Effect of age and sex on human drug metabolism. Br Med J. 1971 Sep 11;3(5775):607–609. doi: 10.1136/bmj.3.5775.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rowland M. Influence of route of administration on drug availability. J Pharm Sci. 1972 Jan;61(1):70–74. doi: 10.1002/jps.2600610111. [DOI] [PubMed] [Google Scholar]
  18. SHERLOCK S., BEARN A. G., BILLING B. H., PATERSON J. C. S. Splanchnic blood flow in man by the bromsulfalein method: the relation of peripheral plasma bromsulfalein level to the calculated flow. J Lab Clin Med. 1950 Jun;35(6):923–932. [PubMed] [Google Scholar]
  19. Saunders L., Natunen T. A four parameter model for oral drug absorption. J Pharm Pharmacol. 1976 Jul;28(7):572–579. doi: 10.1111/j.2042-7158.1976.tb02798.x. [DOI] [PubMed] [Google Scholar]
  20. Shand D. G., Nuckolls E. M., Oates J. A. Plasma propranolol levels in adults with observations in four children. Clin Pharmacol Ther. 1970 Jan-Feb;11(1):112–120. doi: 10.1002/cpt1970111112. [DOI] [PubMed] [Google Scholar]
  21. Shand D. G. Pharmacokinetic properties of the beta-adrenergic receptor blocking drugs. Drugs. 1974;7(1):39–47. doi: 10.2165/00003495-197407010-00003. [DOI] [PubMed] [Google Scholar]
  22. Shand D. G., Rangno R. E., Evans G. H. The disposition of propranolol. II. Hepatic elimination in the rat. Pharmacology. 1972;8(4):344–352. doi: 10.1159/000136352. [DOI] [PubMed] [Google Scholar]
  23. Shand D. G., Rangno R. E. The disposition of propranolol. I. Elimination during oral absorption in man. Pharmacology. 1972;7(3):159–168. doi: 10.1159/000136285. [DOI] [PubMed] [Google Scholar]
  24. Thompson E. N., Williams R. Effect of age on liver function with particular reference to bromsulphalein excretion. Gut. 1965 Jun;6(3):266–269. doi: 10.1136/gut.6.3.266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Vestal R. E., Norris A. H., Tobin J. D., Cohen B. H., Shock N. W., Andres R. Antipyrine metabolism in man: influence of age, alcohol, caffeine, and smoking. Clin Pharmacol Ther. 1975 Oct;18(4):425–432. doi: 10.1002/cpt1975184425. [DOI] [PubMed] [Google Scholar]
  26. WEST C. D., BROWN H., SIMONS E. L., CARTER D. B., KUMAGAI L. F., ENGLERT E., Jr Adrenocortical function and cortisol metabolism in old age. J Clin Endocrinol Metab. 1961 Oct;21:1197–1207. doi: 10.1210/jcem-21-10-1197. [DOI] [PubMed] [Google Scholar]
  27. Wallace S., Whiting B. Factors affecting drug binding in plasma of elderly patients. Br J Clin Pharmacol. 1976 Apr;3(2):327–330. doi: 10.1111/j.1365-2125.1976.tb00611.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wilkinson G. R., Shand D. G. Commentary: a physiological approach to hepatic drug clearance. Clin Pharmacol Ther. 1975 Oct;18(4):377–390. doi: 10.1002/cpt1975184377. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES