Skip to main content
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1991 Sep;32(3):379–385. doi: 10.1111/j.1365-2125.1991.tb03916.x

The interactions between nisoldipine and two beta-adrenoceptor antagonists--atenolol and propranolol.

H L Elliott 1, P A Meredith 1, C McNally 1, J L Reid 1
PMCID: PMC1368535  PMID: 1777376

Abstract

1. The interactions between the dihydropyridine calcium antagonist nisoldipine and two beta-adrenoceptor blocker drugs (atenolol and propranolol) were investigated in two groups of healthy normotensive subjects. 2. The steady state plasma concentrations of both beta-adrenoceptor blockers were significantly altered by the addition of nisoldipine: for propranolol there were significant increases in Cmax, by about 50%, and in AUC by about 30% and for atenolol there was a significant increase in Cmax, by about 20%. 3. The addition of nisoldipine was also associated with significant changes in apparent liver blood flow (measured by indocyanine green clearance) from 1.4 to 2.4 l min-1 in the atenolol group and from 1.3 to 2.3 l min-1 in the propranolol group. 4. Both nisoldipine-beta-adrenoceptor blocker combinations were associated with small enhanced blood pressure reductions e.g. from 104/60 with atenolol alone to 98/50 mm Hg with the combination but there was no alteration to the extent of beta-adrenoceptor blockade (as assessed by bicycle ergometry). 5. This pharmacodynamic profile in healthy normotensives is consistent with the known therapeutic efficacy of such combination treatments in patients with hypertension and angina. 6. It is suggested that there is a pharmacokinetic component to the efficacy of this type of combination, perhaps reflecting vasodilator-induced changes in drug absorption and/or hepatic extraction.

Full text

PDF
379

Selected References

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

  1. Aoki K., Kondo S., Mochizuki A., Yoshida T., Kato S., Kato K., Takikawa K. Antihypertensive effect of cardiovascular Ca2+-antagonist in hypertensive patients in the absence and presence of beta-adrenergic blockade. Am Heart J. 1978 Aug;96(2):218–226. doi: 10.1016/0002-8703(78)90089-3. [DOI] [PubMed] [Google Scholar]
  2. Dargie H. J., Lynch P. G., Krikler D. M., Harris L., Krikler S. Nifedipine and propranolol: a beneficial drug interaction. Am J Med. 1981 Oct;71(4):676–682. doi: 10.1016/0002-9343(81)90238-2. [DOI] [PubMed] [Google Scholar]
  3. De Caprio L., Papa M., Acanfora D., Abete P., Gallucci F., Covelluzzi F., Cicatiello A. M., Rengo F. Acute effects of nisoldipine, propranolol, and their combination in patients with chronic stable angina: a double-blind, randomized, cross-over, placebo-controlled study. J Cardiovasc Pharmacol. 1990 Aug;16(2):325–330. doi: 10.1097/00005344-199008000-00020. [DOI] [PubMed] [Google Scholar]
  4. Ekelund L. G., Orö L. Antianginal efficiency of nifedipine with and without a beta-blocker, studied with exercise test. A double-blind, randomized subacute study. Clin Cardiol. 1979 Jun;2(3):203–211. doi: 10.1002/clc.4960020306. [DOI] [PubMed] [Google Scholar]
  5. Feely J. Nifedipine increases and glyceryl trinitrate decreases apparent liver blood flow in normal subjects. Br J Clin Pharmacol. 1984 Jan;17(1):83–85. doi: 10.1111/j.1365-2125.1984.tb05003.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gangji D., Juvent M., Niset G., Wathieu M., Degreve M., Bellens R., Poortmans J., Degre S., Fitzsimons T. J., Herchuelz A. Study of the influence of nifedipine on the pharmacokinetics and pharmacodynamics of propranolol, metoprolol and atenolol. Br J Clin Pharmacol. 1984;17 (Suppl 1):29S–35S. doi: 10.1111/j.1365-2125.1984.tb02425.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kendall M. J., Jack D. B., Laugher S. J., Lobo J., Rolf Smith S. Lack of a pharmacokinetic interaction between nifedipine and the beta-adrenoceptor blockers metoprolol and atenolol. Br J Clin Pharmacol. 1984 Sep;18(3):331–335. doi: 10.1111/j.1365-2125.1984.tb02472.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Levine M. A., Ogilvie R. I., Leenen F. H. Pharmacokinetic and pharmacodynamic interactions between nisoldipine and propranolol. Clin Pharmacol Ther. 1988 Jan;43(1):39–48. doi: 10.1038/clpt.1988.9. [DOI] [PubMed] [Google Scholar]
  9. Meredith P. A., Pasanisi F., Elliott H. L., Reid J. L. The effect of nisoldipine on apparent liver blood flow and effective renal plasma flow. Br J Clin Pharmacol. 1985 Sep;20(3):235–237. doi: 10.1111/j.1365-2125.1985.tb05066.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Rosenkranz B., Ledermann H., Frölich J. C. Interaction between nifedipine and atenolol: pharmacokinetics and pharmacodynamics in normotensive volunteers. J Cardiovasc Pharmacol. 1986 Sep-Oct;8(5):943–949. doi: 10.1097/00005344-198609000-00010. [DOI] [PubMed] [Google Scholar]
  11. Schoors D. F., Vercruysse I., Musch G., Massart D. L., Dupont A. G. Influence of nicardipine on the pharmacokinetics and pharmacodynamics of propranolol in healthy volunteers. Br J Clin Pharmacol. 1990 May;29(5):497–501. doi: 10.1111/j.1365-2125.1990.tb03671.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Smith S. R., Wilkins M. R., Jack D. B., Kendall M. J., Laugher S. Pharmacokinetic interactions between felodipine and metoprolol. Eur J Clin Pharmacol. 1987;31(5):575–578. doi: 10.1007/BF00606633. [DOI] [PubMed] [Google Scholar]
  13. Vercruysse I., Schoors D. F., Musch G., Massart D. L., Dupont A. G. Nicardipine does not influence the pharmacokinetics and pharmacodynamics of atenolol. Br J Clin Pharmacol. 1990 Sep;30(3):499–500. doi: 10.1111/j.1365-2125.1990.tb03806.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Vinceneux P., Canal M., Domart Y., Roux A., Cascio B., Orofiamma B., Larribaud J., Flouvat B., Carbon C. Pharmacokinetic and pharmacodynamic interactions between nifedipine and propranolol or betaxolol. Int J Clin Pharmacol Ther Toxicol. 1986 Mar;24(3):153–158. [PubMed] [Google Scholar]
  15. Yagil Y., Leibel B., Kobrin I., Stessman J., Ishay D. B. The combination of propranolol and nifedipine in the treatment of hypertension: acute and long term effects. Postgrad Med J. 1983;59 (Suppl 2):114–118. [PubMed] [Google Scholar]
  16. Yee Y. G., Rubin P., Blaschke T. F. Atenolol determination by high-performance liquid chromatography and fluorescence detection. J Chromatogr. 1979 Apr 1;171:357–362. doi: 10.1016/s0021-9673(01)95315-4. [DOI] [PubMed] [Google Scholar]

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

RESOURCES