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British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1984 Dec;18(6):853–860. doi: 10.1111/j.1365-2125.1984.tb02555.x

Failure of 'therapeutic' doses of beta-adrenoceptor antagonists to alter the disposition of tolbutamide and lignocaine.

J O Miners, L M Wing, K J Lillywhite, K J Smith
PMCID: PMC1463673  PMID: 6152176

Abstract

The effects of separate 1 week pre-treatments with each of the beta-adrenoceptor antagonists, propranolol (80 mg every 12 h), metoprolol (100 mg every 12 h) and atenolol (50 mg once daily), on the disposition of a single i.v. dose of tolbutamide were studied in six healthy volunteers. In addition, the effects of a 1 week pre-treatment with metoprolol (100 mg every 12 h) and atenolol (50 mg once daily) on the disposition of orally and i.v. administered lignocaine were determined in seven healthy subjects. Tolbutamide clearance, half-life, volume of distribution and plasma protein binding were not altered by the beta-adrenoceptor blocker pre-treatments. Similarly, neither metoprolol nor atenolol had a significant effect on the systemic clearance, apparent oral clearance or other dispositional parameters of lignocaine. 'Therapeutic' plasma concentrations of the beta-adrenoceptor blockers were confirmed on each study day. It is concluded that the inhibition of oxidative drug metabolism previously reported for lipophilic beta-adrenoceptor blockers may be selective for different forms of cytochrome P450 and possible concentration-dependent.

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Selected References

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  1. 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]
  2. Benet L. Z., Galeazzi R. L. Noncompartmental determination of the steady-state volume of distribution. J Pharm Sci. 1979 Aug;68(8):1071–1074. doi: 10.1002/jps.2600680845. [DOI] [PubMed] [Google Scholar]
  3. Branch R. A., Shand D. G., Wilkinson G. R., Nies A. S. The reduction of lidocaine clearance by dl-propranolol: an example of hemodynamic drug interaction. J Pharmacol Exp Ther. 1973 Feb;184(2):515–519. [PubMed] [Google Scholar]
  4. Chidsey C., Pine M., Favrot L., Smith S., Leonetti G., Morselli P., Zanchetti A. The use of drug concentration measurements in studies of the therapeutic response to propranolol. Postgrad Med J. 1976;52 (Suppl 4):26–32. [PubMed] [Google Scholar]
  5. Conrad K. A., Byers J. M., 3rd, Finley P. R., Burnham L. Lidocaine elimination: effects of metoprolol and of propranolol. Clin Pharmacol Ther. 1983 Feb;33(2):133–138. doi: 10.1038/clpt.1983.20. [DOI] [PubMed] [Google Scholar]
  6. Conrad K. A., Nyman D. W. Effects of metoprolol and propranolol on theophylline elimination. Clin Pharmacol Ther. 1980 Oct;28(4):463–467. doi: 10.1038/clpt.1980.189. [DOI] [PubMed] [Google Scholar]
  7. Daneshmend T. K., Roberts C. J. The short term effects of propranolol, atenolol and labetalol on antipyrine kinetics in normal subjects. Br J Clin Pharmacol. 1982 Jun;13(6):817–820. doi: 10.1111/j.1365-2125.1982.tb01872.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Johnsson G., Regårdh C. G. Clinical pharmacokinetics of beta-adrenoreceptors blockers. Drugs. 1976;11(Suppl 1):111–121. doi: 10.2165/00003495-197600111-00026. [DOI] [PubMed] [Google Scholar]
  11. Keenaghan J. B., Boyes R. N. The tissue distribution, metabolism and excretion of lidocaine in rats, guinea pigs, dogs and man. J Pharmacol Exp Ther. 1972 Feb;180(2):454–463. [PubMed] [Google Scholar]
  12. McAinsh J. Clinical pharmacokinetics of atenolol. Postgrad Med J. 1977;53 (Suppl 3):74–78. [PubMed] [Google Scholar]
  13. Miners J. O., Foenander T., Wanwimolruk S., Gallus A. S., Birkett D. J. The effect of sulphinpyrazone on oxidative drug metabolism in man: inhibition of tolbutamide elimination. Eur J Clin Pharmacol. 1982;22(4):321–326. doi: 10.1007/BF00548400. [DOI] [PubMed] [Google Scholar]
  14. NELSON E., O'REILLY I. Kinetics of carboxytolbutamide excretion following tolbutamide and carboxytolbutamide administration. J Pharmacol Exp Ther. 1961 Apr;132:103–109. [PubMed] [Google Scholar]
  15. Nation R. L., Peng G. W., Chiou W. L. Simple, rapid and micro high-pressure liquid chromatographic method for the simultaneous determination of tolbutamide and carboxy tolbutamide in plasma. J Chromatogr. 1978 Jul 1;146(1):121–131. doi: 10.1016/s0378-4347(00)81296-7. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Ochs H. R., Greenblatt D. J., Woo E., Franke K., Smith T. W. Effect of propranolol on pharmacokinetics and acute electrocardiographic changes following intravenous quinidine in humans. Pharmacology. 1978;17(6):301–306. doi: 10.1159/000136870. [DOI] [PubMed] [Google Scholar]
  18. Ong H., du Souich P., Marchand C. In vivo study of propranolol and metabolite(s) disposition in rat liver. Drug Metab Dispos. 1981 Nov-Dec;9(6):529–534. [PubMed] [Google Scholar]
  19. 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]
  20. Thomas R. C., Ikeda G. J. The metabolic fate of tolbutamide in man and in the rat. J Med Chem. 1966 Jul;9(4):507–510. doi: 10.1021/jm00322a014. [DOI] [PubMed] [Google Scholar]
  21. Tucker G. T., Bax N. D., Lennard M. S., Crewe K., Woods H. F. Lack of effect of atenolol on antipyrine clearance. Br J Clin Pharmacol. 1982 Nov;14(5):743–744. doi: 10.1111/j.1365-2125.1982.tb04967.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Wing L. M., Miners J. O., Birkett D. J., Foenander T., Lillywhite K., Wanwimolruk S. Lidocaine disposition--sex differences and effects of cimetidine. Clin Pharmacol Ther. 1984 May;35(5):695–701. doi: 10.1038/clpt.1984.97. [DOI] [PubMed] [Google Scholar]

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