Skip to main content
SpringerLink
Log in

Vancomycin

A Review of Population Pharmacokinetic Analyses

  • Review Article
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Abstract

Despite nearly five decades of clinical use, vancomycin has retained a significant and uncontested niche in the antibacterial arsenal because of its consistent activity against almost all Gram-positive bacteria. Nevertheless, major vancomycin toxicities have been reported in the literature — in particular, nephrotoxicity and ototoxicity. Vancomycin pharmacokinetics have been described in numerous studies for 25 years. This review presents a synthesis of the reported population pharmacokinetic models of vancomycin. The objective was to determine if there was a consensus on a structural model and which covariates were identified. A literature search was conducted from the PubMed database, from its inception through December 2010, using the following terms: ‘vancomycin’, ‘pharmacokinetic(s)’, ‘population’, ‘model(ling)’ and ‘nonlinear mixed effect’. Articles were excluded if they were not pertinent. The reference lists of all selected articles were also evaluated.

Twenty-five articles were included in this review: 15 models concerned paediatric patients and ten models were conducted in adults. In neonates and infants, the pharmacokinetics of vancomycin were mainly described by a one-compartment model, whereas in adults, a two-compartment model was preferentially used. Various covariates were tested but only three (age, creatinine clearance [CLCR] and body weight) were included in almost all of the described models. After inclusion of these covariates, the mean (range) values of the interindividual variability in the clearance and volume of distribution were 30% (15.6–45%) and 23% (12.6–48%), respectively. The mean (range) value of the residual variability was 20% (7–39.6%).

This review highlights the numerous population pharmacokinetic models of vancomycin developed in recent decades and concludes with relevant information for clinicians and researchers. To optimize vancomycin dosage, this review points out the relevant covariates according to the target population. In adults, dosage optimization depends on CLCR and body weight, while in children, it depends on age, body weight and CLCR. For future population pharmacokinetic studies, a sensitive liquid chromatography-tandem mass spectrometry method could be used and new covariates such as cardiac output or possible renal transporters could be tested. Finally, we suggest that external evaluation should be the first step in a pharmacokinetic analysis of vancomycin rather than describing a new model.

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

Table I
Table II
Table III
Table IV
Table V

Similar content being viewed by others

References

  1. Levine DP. Vancomycin: a history. Clin Infect Dis 2006; 42: S5–12

    Article  PubMed  CAS  Google Scholar 

  2. De Hoog M, Mouton JW, van den Anker JN. New dosing strategies for antibacterial agents in the neonate. Semin Fetal Neonatal Med 2005; 10: 185–94

    Article  PubMed  Google Scholar 

  3. Matzke GR, Zhanel GG, Guay DR. Clinical pharmacokinetics of vancomycin. Clin Pharmacokinet 1986; 11: 257–82

    Article  PubMed  CAS  Google Scholar 

  4. Oudin C, Vialet R, Boulamery A, et al. Vancomycin prescription in neonates and young infants: toward a simplified dosage. Arch Dis Child Fetal Neonatal Ed 2011; 96: F365–70

    Article  PubMed  CAS  Google Scholar 

  5. Marques-Minana MR, Saadeddin A, Peris JE. Population pharmacokinetic analysis of vancomycin in neonates: a new proposal of initial dosage guideline. Br J Clin Pharmacol 2010; 70: 713–20

    Article  PubMed  CAS  Google Scholar 

  6. Lo YL, van Hasselt JGC, Heng SC, et al. Population pharmacokinetics of vancomycin in premature Malaysian neonates: identification of predictors for dosing determination. Antimicrob Agents Chemother 2010; 54: 2626–32

    Article  PubMed  CAS  Google Scholar 

  7. Anderson BJ, Allegaert K, van den Anker JN, et al. Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance. Br J Clin Pharmacol 2007; 63: 75–84

    Article  PubMed  CAS  Google Scholar 

  8. Kimura T, Sunakawa K, Matsuura N, et al. Population pharmacokinetics of abekacin, vancomycin, and panipenem in neonates. Antimicrob Agents Chemother 2004; 48: 1159–67

    Article  PubMed  CAS  Google Scholar 

  9. Capparelli EV, Lane JR, Romanowski GL, et al. The influence of renal function and maturation on vancomycin elimination in newborns and infants. J Clin Pharmacol 2001; 41: 927–34

    Article  PubMed  CAS  Google Scholar 

  10. Wrishko RE, Levine M, Khoo D, et al. Vancomycin pharmacokinetics and Bayesian estimation in paediatric patients. Ther Drug Monit 2000; 22: 522–31

    Article  PubMed  CAS  Google Scholar 

  11. Lamarre P, Lebel D, Ducharme MP. Population pharmacokinetic model for vancomycin in paediatric patients and its predictive value in a naive population. Antimicrob Agents Chemother 2000; 44: 278–82

    Article  PubMed  CAS  Google Scholar 

  12. De Hoog M, Schoemaker RC, Mouton JW, et al. Vancomycin population pharmacokinetics. Clin Pharmacol Ther 2000; 67: 360–7

    Article  PubMed  Google Scholar 

  13. Grimsley C, Thomson AH. Pharmacokinetics and dose requirements of vancomycin in neonates. Arch Dis Child Fetal Neonatal Ed 1999; 81: 221–7

    Article  Google Scholar 

  14. Yasuhara M, Iga T, Zenda H, et al. Population pharmacokineics of vancomycin in Japanese paediatric patients. Ther Drug Monit 1998; 20: 612–8

    Article  PubMed  CAS  Google Scholar 

  15. Silva R, Reis E, Bispo MA, et al. The kinetic profile of vancomycin in neonates. J Pharm Pharmacol 1998; 50: 1255–60

    Article  PubMed  CAS  Google Scholar 

  16. Seay RE, Brundage RC, Jensen PD, et al. Population pharmacokinetics of vancomycin in neonates. Clin Pharmacol Ther 1994; 56: 169–75

    Article  PubMed  CAS  Google Scholar 

  17. Asbury WH, Darsey EH, Rose WB, et al. Vancomycin pharmacokinetics in neonates and infants: a retrospective evaluation. Ann Pharmacother 1993; 27: 490–6

    PubMed  CAS  Google Scholar 

  18. Schaible DH, Rocci ML, Alpert GA, et al. Vancomycin pharmacokinetics in infants: relationships to indices of maturation. Pediatr Infect Dis 1986; 5: 304–8

    Article  PubMed  CAS  Google Scholar 

  19. Revilla N, Martin-Suarez A, Perez MP, et al. Vancomycin dosing assessment in intensive care unit patients based on a population pharmacokinetic/pharmacodynamic simulation. Br J Clin Pharmacol 2010; 70: 201–12

    Article  PubMed  CAS  Google Scholar 

  20. Sanchez JL, Dominguez AR, Lane JR, et al. Population pharmacokinetics of vancomycin in adult and geriatric patients: comparison of eleven approaches. Int J Clin Pharmacol Ther 2010; 48: 525–33

    PubMed  CAS  Google Scholar 

  21. Tanaka A, Aiba T, Otsuka T, et al. Population pharmacokinetic analysis of vancomycin using serum cystatin C as a marker of renal function. Antimicrob Agents Chemother 2010; 54: 778–82

    Article  PubMed  CAS  Google Scholar 

  22. Dolton M, Xu H, Cheong E, et al. Vancomycin pharmacokinetics in patients with severe burn injuries. Burns 2010; 36: 469–76

    Article  PubMed  Google Scholar 

  23. Yamamoto M, Kuzuya T, Baba H, et al. Population pharmacokinetic analysis of vancomycin in patients with Gram-positive infections and the influence of infectious disease type. J Clin Phar Ther 2009; 34: 473–83

    Article  CAS  Google Scholar 

  24. Llopis-Salvia P, Jimenez-Torres NV. Population pharmacokinetic parameters of vancomycin in critically ill patients. J Clin Pharm Ther 2006; 31: 447–54

    Article  PubMed  CAS  Google Scholar 

  25. Staatz CE, Byrne C, Thomson AH. Population pharmacokinetic modelling of gentamicin and vancomycin in patients with unstable renal function following cardiothoracic surgery. Br J Clin Pharmacol 2005; 61: 164–74

    Article  Google Scholar 

  26. Buelga DS, Fernandez de Gatta M, Herrera EV, et al. Population pharmacokinetic analysis of vancomycin in patients with hematological malignancies. Antimicrob Agents Chemother 2005; 49: 4934–41

    Article  PubMed  CAS  Google Scholar 

  27. Mulla H, Pooboni S. Population pharmacokinetics of vancomycin in patients receiving extracorporeal membrane oxygenation. Br J Clin Pharmacol 2005; 60: 265–75

    Article  PubMed  CAS  Google Scholar 

  28. Yasuhara M, Iga T, Zenda H, et al. Population pharmacokineics of vancomycin in Japanese adult patients. Ther Drug Monit 1998; 20: 139–48

    Article  PubMed  CAS  Google Scholar 

  29. Kildoo CW, Lin LM, Gabriel MH, et al. Vancomycin pharmacokinetics in infants: relationship to postconceptional age and serum creatinine. Dev Pharmacol Ther 1989; 14: 77–83

    PubMed  CAS  Google Scholar 

  30. Ohnishi A, Yano Y, Ishibashi T, et al. Evaluation of Bayesian predictability of vancomycin concentration using population pharmacokinetic parameters in pediatric patients. Drug Metab Pharmacokinet 2005; 20: 415–22

    Article  PubMed  CAS  Google Scholar 

  31. Paap CM, Nahata MC. Clinical pharmacokinetics of antibacterial drugs in neonates. Clin Pharmacokinet 1990; 19: 280–318

    Article  PubMed  CAS  Google Scholar 

  32. Shaffer SG, Bradt SK, Meade VM, et al. Extracellular fluid volume changes in very low birth weight infants during first 2 postnatal months. J Pediatr 1987; 111: 124–8

    Article  PubMed  CAS  Google Scholar 

  33. West GB, Brown JH, Enquist BJ. A general model for the origin of allometric scaling laws in biology. Science 1997; 276: 122–6

    Article  PubMed  CAS  Google Scholar 

  34. Anderson BJ, Holford NHG. Mechanism-based concepts of size and maturity in pharmacokinetics. Annu Rev Pharmacol Toxicol 2008; 48: 303–32

    Article  PubMed  CAS  Google Scholar 

  35. Guignard JP, Drukker A. Why do newborn infants have a high plasma creatinine? Pediatrics 1999; 103: e49

    Article  PubMed  CAS  Google Scholar 

  36. Fernandez de Gatta MM, Santos Buelga D, Sanchez-Navarro A, et al. Vancomycin dosage optimization in patients with malignant haematological disease by pharmacokinetic/pharmacodynamic analysis. Clin Pharmacokinet 2009; 48: 1–8

    Article  Google Scholar 

  37. Ducharme MP, Slaughter RL, Edwards DJ. Vancomycin pharmacokinetics in patient population: effect of age, gender and body weight. Ther Drug Monit 1994; 16: 513–8

    Article  PubMed  CAS  Google Scholar 

  38. Culter NR, Naravag PK, Lesko JL, et al. Vancomycin disposition: the importance of age. Clin Pharmacol Ther 1984; 36: 803–10

    Article  Google Scholar 

  39. Vance-Bryan K, Rostchafer JC, Gilliard SS, et al. A comparative assessment of vancomycin-associated nephrotoxicity in the young versus elderly hospitalized patient. J Antimicrob Chemother 1994; 33: 811–21

    Article  PubMed  CAS  Google Scholar 

  40. Fanos V, Cataldi L. Renal transport of antibiotics and nephrotoxicity: a review. J Chemother 2001; 13: 461–72

    PubMed  CAS  Google Scholar 

  41. Golper TA, Noonan HM, Elzinga L, et al. Vancomycin pharmacokinetics, renal handling, and nonrenal clearances in normal human subjects. Clin Pharmacol Ther 1988; 43: 565–70

    Article  PubMed  CAS  Google Scholar 

  42. Sokol PP. Mechanism of vancomycin transport in the kidney: studies in rabbit renal brush border and basolateral membrane vesicles. J Pharmacol Exp Ther 1991; 259: 1283–7

    PubMed  CAS  Google Scholar 

Download references

Acknowledgement

No sources of funding were used to prepare this review. The authors declare no potential conflicts of interest.

Author information

Authors and Affiliations

  1. Laboratoire de Pharmacologie Médicale et Clinique, Faculté de Médecine Timone, Aix Marseille Université, Marseille, France

    Amélie Marsot, Audrey Boulamery, Bernard Bruguerolle & Nicolas Simon

Authors
  1. Amélie Marsot
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Audrey Boulamery
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bernard Bruguerolle
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nicolas Simon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amélie Marsot.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marsot, A., Boulamery, A., Bruguerolle, B. et al. Vancomycin. Clin Pharmacokinet 51, 1–13 (2012). https://doi.org/10.2165/11596390-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11596390-000000000-00000

Keywords

Search

Navigation