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British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1987 Jan;23(1):41–46. doi: 10.1111/j.1365-2125.1987.tb03007.x

Quantitative and qualitative binding characteristics of disopyramide in serum from patients with decreased renal and hepatic function.

L E Pedersen, J Bonde, N A Graudal, N V Backer, J E Hansen, J P Kampmann
PMCID: PMC1386138  PMID: 3814461

Abstract

Protein binding of disopyramide, binding capacities, affinity constants and serum concentrations of alpha 1-acid glycoprotein (AAG) were studied in five groups of patients. A: young healthy volunteers (n = 8); B: elderly patients with minor symptoms of ischaemic heart disease (n = 9); C: patients with cirrhosis of the liver and normal values of coagulation factors (II, VII and X), albumin and immunoglobulin G (n = 8); D: patients with cirrhosis and at least two abnormal of the previously mentioned values (n = 9) and E: eleven patients with severely impaired renal function. Subfractions of AAG (Fr1, Fr2 and Fr3) were determined by affinoimmunoelectrophoresis. AAG concentration was significantly (P less than 0.005) elevated in group E patients and decreased (P less than 0.025) in group D patients. Fr2 is probably associated with the high affinity, first binding site of disopyramide to AAG. Earlier observations of a reduced qualitative binding of disopyramide in patients with cirrhosis can be explained by a significant decrease in Fr2 (P less than 0.001) in group D patients. The protein binding of disopyramide in patients with uraemia was significantly increased due to a significant (P less than 0.005) increase in AAG concentration in spite of a smaller (P less than 0.025) affinity constant. Suggestions for therapeutic drug monitoring based on total serum concentrations are given.

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Selected References

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  1. Barre J., Houin G., Rosenbaum J., Zini R., Dhumeaux D., Tillement J. P. Decreased alpha 1-acid glycoprotein in liver cirrhosis: consequences for drug protein binding. Br J Clin Pharmacol. 1984 Oct;18(4):652–653. doi: 10.1111/j.1365-2125.1984.tb02525.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bonde J., Pedersen L. E., Bødtker S., Angelo H. R., Svendsen T. L., Kampmann J. P. The influence of age and smoking on the elimination of disopyramide. Br J Clin Pharmacol. 1985 Nov;20(5):453–458. doi: 10.1111/j.1365-2125.1985.tb05096.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bredesen J. E., Kierulf P. Relationship between alpha 1-acid glycoprotein and plasma binding of disopyramide and mono-N-dealkyldisopyramide. Br J Clin Pharmacol. 1984 Nov;18(5):779–784. doi: 10.1111/j.1365-2125.1984.tb02542.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cleve H., Strohmeyer G. Quantitative Variationen von Serumglykoproteinen bei pathologischen Prozessen; Bestimmng von saurem alpha-1-Glycoprotein, Gc und alpha-2-Makroglobulin mit der radialen Immunodiffusion. Klin Wochenschr. 1967 Oct 15;45(20):1051–1054. doi: 10.1007/BF01727819. [DOI] [PubMed] [Google Scholar]
  5. Cunningham J. L., Shen D. D., Shudo I., Azarnoff D. L. The effects of urine pH and plasma protein binding on the renal clearance of disopyramide. Clin Pharmacokinet. 1977 Sep-Oct;2(5):373–383. doi: 10.2165/00003088-197702050-00004. [DOI] [PubMed] [Google Scholar]
  6. Davis D., Grossman S. H., Kitchell B. B., Shand D. G., Routledge P. A. The effects of age and smoking on the plasma protein binding of lignocaine and diazepam. Br J Clin Pharmacol. 1985 Feb;19(2):261–265. doi: 10.1111/j.1365-2125.1985.tb02641.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Grossman S. H., Davis D., Kitchell B. B., Shand D. G., Routledge P. A. Diazepam and lidocaine plasma protein binding in renal disease. Clin Pharmacol Ther. 1982 Mar;31(3):350–357. doi: 10.1038/clpt.1982.45. [DOI] [PubMed] [Google Scholar]
  8. Haughey D. B., Kraft C. J., Matzke G. R., Keane W. F., Halstenson C. E. Protein binding of disopyramide and elevated alpha-1-acid glycoprotein concentrations in serum obtained from dialysis patients and renal transplant recipients. Am J Nephrol. 1985;5(1):35–39. doi: 10.1159/000166900. [DOI] [PubMed] [Google Scholar]
  9. Hiramatsu S., Kojima J., Okada T. T., Inai S., Ohmori K. The serum protein profile in chronic hepatitis, cirrhosis and liver cancer. Acta Hepatogastroenterol (Stuttg) 1976 Jun;23(3):177–182. [PubMed] [Google Scholar]
  10. Rosenthal H. E. A graphic method for the determination and presentation of binding parameters in a complex system. Anal Biochem. 1967 Sep;20(3):525–532. doi: 10.1016/0003-2697(67)90297-7. [DOI] [PubMed] [Google Scholar]
  11. Weeke B., Weeke E., Bendixen G. The variation in twenty-one serum proteins before and after renal transplantation. I. General pattern. Acta Med Scand. 1971 Jan-Feb;189(1-2):113–118. doi: 10.1111/j.0954-6820.1971.tb04349.x. [DOI] [PubMed] [Google Scholar]

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