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. 1993 May;37(5):1132–1136. doi: 10.1128/aac.37.5.1132

Serum protein-binding characteristics of vancomycin.

H Sun 1, E G Maderazo 1, A R Krusell 1
PMCID: PMC187916  PMID: 8517702

Abstract

A synthesis of studies of serum protein binding of vancomycin and its reported abnormal binding in serum with very high concentrations of immunoglobulin A (IgA) suggests that this antibiotic may be bound to more than one serum protein. Using an ultrafiltration method for separating free from bound drug and high-performance liquid chromatography to measure drug concentration, we studied the binding characteristics of vancomycin for alpha-1 acid glycoprotein, IgG, IgM, IgA, and albumin. The results showed that vancomycin does not bind to alpha-1 acid glycoprotein, IgG, or IgM. Major binding to albumin and IgA occurs, and total drug binding to serum proteins can be fully explained by binding to these two proteins. We calculated an N (number of binding sites per molecule) of 1.3 +/- 0.4 and a K (association constant) of 3.3 x 10(5) +/- 6.3 x 10(4) M-1 (NK = 4.3 x 10(5) M-1) for binding to IgA, whereas the corresponding NK value for albumin was only 527.5 M-1, indicating that vancomycin preferentially binds to IgA. Very high concentrations of IgA in serum (i.e., grams per deciliter), such as in patients with IgA myeloma, may result in the paradox of high (total) concentrations of vancomycin in serum that may be clinically ineffective.

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Selected References

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

  1. Ackerman B. H., Taylor E. H., Olsen K. M., Abdel-Malak W., Pappas A. A. Vancomycin serum protein binding determination by ultrafiltration. Drug Intell Clin Pharm. 1988 Apr;22(4):300–303. doi: 10.1177/106002808802200404. [DOI] [PubMed] [Google Scholar]
  2. Boxenbaum H. G., Riegelman S., Elashoff R. M. Statistical estimations in pharmacokinetics. J Pharmacokinet Biopharm. 1974 Apr;2(2):123–148. doi: 10.1007/BF01061504. [DOI] [PubMed] [Google Scholar]
  3. Cantú T. G., Dick J. D., Elliott D. E., Humphrey R. L., Kornhauser D. M. Protein binding of vancomycin in a patient with immunoglobulin A myeloma. Antimicrob Agents Chemother. 1990 Jul;34(7):1459–1461. doi: 10.1128/aac.34.7.1459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cutler N. R., Narang P. K., Lesko L. J., Ninos M., Power M. Vancomycin disposition: the importance of age. Clin Pharmacol Ther. 1984 Dec;36(6):803–810. doi: 10.1038/clpt.1984.260. [DOI] [PubMed] [Google Scholar]
  5. Jehl F., Gallion C., Thierry R. C., Monteil H. Determination of vancomycin in human serum by high-pressure liquid chromatography. Antimicrob Agents Chemother. 1985 Apr;27(4):503–507. doi: 10.1128/aac.27.4.503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Krogstad D. J., Moellering R. C., Jr, Greenblatt D. J. Single-dose kinetics of intravenous vancomycin. J Clin Pharmacol. 1980 Apr;20(4 Pt 1):197–201. doi: 10.1002/j.1552-4604.1980.tb01696.x. [DOI] [PubMed] [Google Scholar]
  7. Lindholm D. D., Murray J. S. Persistence of vancomycin in the blood during renal failure and its treatment by hemodialysis. N Engl J Med. 1966 May 12;274(19):1047–1051. doi: 10.1056/NEJM196605122741902. [DOI] [PubMed] [Google Scholar]
  8. Matzke G. R., McGory R. W., Halstenson C. E., Keane W. F. Pharmacokinetics of vancomycin in patients with various degrees of renal function. Antimicrob Agents Chemother. 1984 Apr;25(4):433–437. doi: 10.1128/aac.25.4.433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Matzke G. R., Zhanel G. G., Guay D. R. Clinical pharmacokinetics of vancomycin. Clin Pharmacokinet. 1986 Jul-Aug;11(4):257–282. doi: 10.2165/00003088-198611040-00001. [DOI] [PubMed] [Google Scholar]
  10. McClain J. B., Bongiovanni R., Brown S. Vancomycin quantitation by high-performance liquid chromatography in human serum. J Chromatogr. 1982 Sep 10;231(2):463–466. doi: 10.1016/s0378-4347(00)81873-3. [DOI] [PubMed] [Google Scholar]
  11. Priore R. L., Rosenthal H. E. A statistical method for the estimation of binding parameters in a complex system. Anal Biochem. 1976 Jan;70(1):231–240. doi: 10.1016/s0003-2697(76)80063-2. [DOI] [PubMed] [Google Scholar]
  12. Rodvold K. A., Blum R. A., Fischer J. H., Zokufa H. Z., Rotschafer J. C., Crossley K. B., Riff L. J. Vancomycin pharmacokinetics in patients with various degrees of renal function. Antimicrob Agents Chemother. 1988 Jun;32(6):848–852. doi: 10.1128/aac.32.6.848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Rotschafer J. C., Crossley K., Zaske D. E., Mead K., Sawchuk R. J., Solem L. D. Pharmacokinetics of vancomycin: observations in 28 patients and dosage recommendations. Antimicrob Agents Chemother. 1982 Sep;22(3):391–394. doi: 10.1128/aac.22.3.391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sophianopoulos J. A., Durham S. J., Sophianopoulos A. J., Ragsdale H. L., Cropper W. P., Jr Ultrafiltration is theoretically equivalent to equilibrium dialysis but much simpler to carry out. Arch Biochem Biophys. 1978 Apr 15;187(1):132–137. doi: 10.1016/0003-9861(78)90015-2. [DOI] [PubMed] [Google Scholar]
  16. Wittendorf R. W., Swagzdis J. E., Gifford R., Mico B. A. Protein binding of glycopeptide antibiotics with diverse physical-chemical properties in mouse, rat, and human serum. J Pharmacokinet Biopharm. 1987 Feb;15(1):5–13. doi: 10.1007/BF01062935. [DOI] [PubMed] [Google Scholar]

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