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. 1984 Apr;17(4):405–409. doi: 10.1111/j.1365-2125.1984.tb02364.x

Pethidine binding in whole blood: methodology and clinical significance.

C La Rosa, D J Morgan, L E Mather
PMCID: PMC1463408  PMID: 6721986

Abstract

A three-compartment equilibrium dialysis method was developed for the simultaneous and direct determination of drug binding in whole blood and in plasma and of the blood to plasma concentration ratio (b/p). The unbound fraction of pethidine in the blood of six healthy volunteers (0.63, s.d. 0.09, n = 23 determinations) was significantly different from that in the blood of six patients (0.72, s.d. 0.08, n = 24 determinations). There was no significant difference in the b/p of six patients (0.84, s.d. 0.09, n = 24 determinations) and six volunteers (0.90, s.d. 0.14, n = 23 determinations). The observed unbound fraction of pethidine in blood (0.6 to 0.7) was considerably lower than previously reported. As this value for the unbound fraction (0.6 to 0.7) is similar to the reported estimated hepatic extraction ratio of the drug in man, it is proposed that pethidine elimination should be described as 'capacity limited, binding sensitive' rather than 'flow-limited'.

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Selected References

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

  1. Austin K. L., Stapleton J. V., Mather L. E. Pethidine clearance during continuous intravenous infusions in postoperative patients. Br J Clin Pharmacol. 1981 Jan;11(1):25–30. doi: 10.1111/j.1365-2125.1981.tb01097.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bickel M. H. Binding of chlorpromazine and imipramine to red cells, albumin, lipoproteins and other blood components. J Pharm Pharmacol. 1975 Oct;27(10):733–738. doi: 10.1111/j.2042-7158.1975.tb09392.x. [DOI] [PubMed] [Google Scholar]
  3. Blaschke T. F. Protein binding and kinetics of drugs in liver diseases. Clin Pharmacokinet. 1977 Jan-Feb;2(1):32–44. doi: 10.2165/00003088-197702010-00003. [DOI] [PubMed] [Google Scholar]
  4. Borondy P., Dill W. A., Chang T., Buchanan R. A., Glazko A. J. Effect of protein binding on the distribution of 5,5-diphenylhydantoin between plasma and red cells. Ann N Y Acad Sci. 1973 Nov 26;226:82–87. doi: 10.1111/j.1749-6632.1973.tb20470.x. [DOI] [PubMed] [Google Scholar]
  5. Bratlid D. Bilirubin binding by human erythrocytes. Scand J Clin Lab Invest. 1972 Feb;29(1):91–97. doi: 10.3109/00365517209081060. [DOI] [PubMed] [Google Scholar]
  6. Cruze C. A., Meyer M. C. Binding of salicylate and sulfathiazole by whole blood constituents. J Pharm Sci. 1976 Jan;65(1):33–37. doi: 10.1002/jps.2600650105. [DOI] [PubMed] [Google Scholar]
  7. Ehrnebo M., Agurell S., Boréus L. O., Gordon E., Lönroth U. Pentazocine binding to blood cells and plasma proteins. Clin Pharmacol Ther. 1974 Sep;16(3):424–429. doi: 10.1002/cpt1974163part1424. [DOI] [PubMed] [Google Scholar]
  8. Ehrnebo M., Odar-Cederlöf I. Binding of amobarbital, pentobarbital and diphenylhydantoin to blood cells and plasma proteins in healthy volunteers and uraemic patients. Eur J Clin Pharmacol. 1975 Aug 14;8(6):445–453. doi: 10.1007/BF00562320. [DOI] [PubMed] [Google Scholar]
  9. Gazzard B. G., Ford-Hutchinson A. W., Smith M. J., Williams R. The binding of paracetamol to plasma proteins of man and pig. J Pharm Pharmacol. 1973 Dec;25(12):964–967. doi: 10.1111/j.2042-7158.1973.tb09987.x. [DOI] [PubMed] [Google Scholar]
  10. Kurata D., Wilkinson G. R. Erythrocyte uptake and plasma binding of diphenylhydantoin. Clin Pharmacol Ther. 1974 Aug;16(2):355–362. doi: 10.1002/cpt1974162355. [DOI] [PubMed] [Google Scholar]
  11. La Rosa C., Mather L. E., Morgan D. J. Pethidine binding in plasma: effects of methodological variables. Br J Clin Pharmacol. 1984 Apr;17(4):411–415. doi: 10.1111/j.1365-2125.1984.tb02365.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. McArthur J. N., Dawkins P. D., Smith M. J. The binding of indomethacin, salicylate and phenobarbitone to human whole blood in vitro. J Pharm Pharmacol. 1971 Jan;23(1):32–36. doi: 10.1111/j.2042-7158.1971.tb12777.x. [DOI] [PubMed] [Google Scholar]
  13. Meyer M. C., Guttman D. E. Novel method for studying protein binding. J Pharm Sci. 1968 Sep;57(9):1627–1629. doi: 10.1002/jps.2600570939. [DOI] [PubMed] [Google Scholar]
  14. Nation R. L. Meperidine binding in maternal and fetal plasma. Clin Pharmacol Ther. 1981 Apr;29(4):472–479. doi: 10.1038/clpt.1981.65. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Taylor E. A., Turner P. The distribution of propranolol, pindolol and atenolol between human erythrocytes and plasma. Br J Clin Pharmacol. 1981 Oct;12(4):543–548. doi: 10.1111/j.1365-2125.1981.tb01263.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Verbeeck R. K., Branch R. A., Wilkinson G. R. Meperidine disposition in man: influence of urinary pH and route of administration. Clin Pharmacol Ther. 1981 Nov;30(5):619–628. doi: 10.1038/clpt.1981.213. [DOI] [PubMed] [Google Scholar]

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