Skip to main content
SpringerLink
Log in

Metabolism of procainamide in patients with chronic heart failure, chronic respiratory failure and chronic renal failure

  • Originals
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Summary

Fractional hydrolysis and acetylation of procainamide, acetylation of procainamide-derived p-aminobenzoic acid and plasma hydrolysis of procaine were studied in 20 patients with chronic heart failure (CHF), 20 patients with chronic respiratory insufficiency (CRI) and 20 patients with chronic renal failure (RF). The results were compared with those obtained in a group of 20 normal volunteers. Hydrolysis of procainamide and procaine were reduced in patients with CHF and CRI, but not in patients with RF. Moreover, more marked decreases in procainamide and procaine hydrolysis were seen in subgroups with secondary hepatic dysfunction. The diminution of hydrolysis of procainamide was not paralleled by changes in acetylation of procainamide or p-aminobenzoic acid. It is concluded that in patients with hepatic involvement secondary to advanced CHF or CRI, hepatic and plasmatic hydrolysis activity is decreased to a degree equivalent to primary liver failure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Koch-Weser, J.: Pharmacokinetics of procainamide in man. Ann. N. Y. Acad. Sci.179, 370–382 (1971)

    Google Scholar 

  2. Souich, P. du, Erill, S.: Metabolism of procainamide and p-aminobenzoic acid in patients with chronic liver disease. Clin. Pharmacol. Ther.22, 588–595 (1977)

    Google Scholar 

  3. Benowitz, N. L., Meister, W.: Pharmacokinetics in patients with cardiac failure. Clin. Pharmacokinet1, 389–405 (1976)

    Google Scholar 

  4. Koch-Weser, J., Klein, S. W.: Procainamide dosage schedules, plasma concentrations, and clinical effects. J. Am. Med. Ass.215, 1454–1460 (1971)

    Google Scholar 

  5. Giardina, E.-G. V., Dreyfuss, J., Bigger, J. T., Shaw, J. M., Schreiber, E. C.: Metabolism of procainamide in normal and cardiac subjects. Clin. Pharmacol. Ther.19, 339–351 (1976)

    Google Scholar 

  6. Montgomery, M. R., Rubin, R. J.: Oxygenation during inhibition of drug metabolism by carbon monoxide or hypoxic hypoxia. J. Appl. Physiol.35, 505–509 (1973)

    Google Scholar 

  7. Cumming, J. F., Mannering, G. J.: Effect of phenobarbital administration on the oxygen requirement for hexobarbital metabolism in the isolated, perfused rat liver and in the intact rat. Biochem. Pharmacol.19, 973–978 (1970)

    Google Scholar 

  8. Roth, R. A., Jr., Rubin, R. J.: Role of blood flow in carbon monoxide and hypoxic hypoxia-induced alterations in hexobarbital metabolism in rats. Drug Metab. Dispos.4, 460–467 (1976)

    Google Scholar 

  9. Cumming, J. F.: The effect of arterial oxygen tension on antipyrine half-time in plasma. Clin. Pharmacol. Ther.19, 468–471 (1976)

    Google Scholar 

  10. Reidenberg, M. M., Kostenbauder, H., Adama, W. P.: Rate of drug metabolism in obese volunteers before and during starvation and in azotemic patients. Metabolism18, 209–213 (1969)

    Google Scholar 

  11. Reidenberg, M. M.: Effect of kidney disease on pharmacokinetics and drug response in Pharmacology and the Future of Man, Vol. 3, Problems of Therapy. Proc. 5th Int. Congr. Pharmacology, San Francisco, 1972, (ed. Okita, G. T., Adreson, G. H.) p 174. Basel, New York: S. Karger 1973

    Google Scholar 

  12. Schröder, H.: Simplified method for determining acetylator phenotype. Br. Med. J.III, 506–507 (1972)

    Google Scholar 

  13. Souich, P. du, Erill, S.: Patterns of acetylation of procainamide and procainamide-derived p-aminobenzoic acid in man. Europ. J. Clin. Pharmacol.10, 283–287 (1976)

    Google Scholar 

  14. Reidenberg, M. M., James, M., Dring, L. G.: The rate of procaine hydrolysis in serum of normal subjects and diseased patients. Clin. Pharmacol. Ther.13, 279–284 (1972)

    Google Scholar 

  15. Gibson, T. P., Matusik, E. J., Briggs, W. A.: N-acetylprocainamide levels in patients with end-stage renal failure. Clin. Pharmacol. Ther.19, 206–212 (1976)

    Google Scholar 

  16. Atkinson, A. J., Krumlovsky, F. A., Huang, C. M., del Greco, F.: Hemodialysis for severe procainamide toxicity: Clinical and pharmacokinetic observations. Clin. Pharmacol. Ther.20, 585–592 (1976)

    Google Scholar 

  17. Karlsson, E., Molin, L., Norlander, B., Sjoqvist, F.: Acetylation of procainamide in man studied with a new gas chromatographic method. Br. J. Clin. Pharmacol.1, 467–475 (1976)

    Google Scholar 

  18. Ferrer, M. J.: Cor pulmonale (pulmonary heart disease): Present day status. Am. Heart. J.89, 657–664 (1975)

    Google Scholar 

  19. Reidenberg, M. M., Drayer, D. E., Levy, M., Warner, H.: Polymorphic acetylation of procainamide in man. Clin. Pharmacol. Ther.17, 722–730 (1975)

    Google Scholar 

  20. Ellard, G. A.: Variations between individuals and populations in the acetylation of isoniazid and its significance for the treatment of pulmonary tuberculosis. Clin. Pharmacol. Ther.19, 610–625 (1976)

    Google Scholar 

  21. Lima, J. J., Jusko, W. J.: Determination of procainamide acetylator status. Clin. Pharmacol. Ther.23, 25–29 (1978)

    Google Scholar 

  22. Talseth, T., Landmark, K. H.: Polymorphic acetylation of sulphadimidine in normal and uremic man. Europ. J. Clin. Pharmacol.11, 33–36 (1977)

    Google Scholar 

  23. Simon, N. M. del Greco, F., Dietz, A. A., Rubinstein, H. M.: Serum cholinesterase deficiency in renal failure. Trans. Am. Soc. Artif. Intern. Organs15, 328–331 (1969)

    Google Scholar 

  24. McArdle, B.: The serum choline esterase in jaundice and diseases of the liver. Quart. J. Med.9, 107–127 (1940)

    Google Scholar 

  25. Drucker, M. M., Blondheim, S. H., Wislicki, L.: Factors affecting acetylation in vivo of para-aminobenzoic acid by human subjects. Clin. Sci.27, 133–141 (1964)

    Google Scholar 

Download references

Author information

Author notes

  1. P. du Souich

    Present address: Département de Pharmacologie Faculté de Médecine, Université de Montréal, H3C 3J7, Montréal, P. Q., Canada

  2. S. Erill

    Present address: Departamento de Farmacologia, Universidad de Bilbao, Spain

Authors and Affiliations

  1. Departamento de Farmacologia y Terapéutica, Universidad Autónoma de Barcelona, Barcelona, Spain

    P. du Souich & S. Erill

Authors
  1. P. du Souich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Erill
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported in part by a grant from Centre de Recherche Merrell International.

Recipient of a Merck Sharp & Dohme International Fellowship in Clinical Pharmacology.

Rights and permissions

Reprints and permissions

About this article

Cite this article

du Souich, P., Erill, S. Metabolism of procainamide in patients with chronic heart failure, chronic respiratory failure and chronic renal failure. Eur J Clin Pharmacol 14, 21–27 (1978). https://doi.org/10.1007/BF00560254

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00560254

Key words

Search

Navigation