Journal of Research in Pharmacy Practice

Predictive performance of Vancomycin population pharmacokinetic models in Iranian patients underwent hematopoietic stem cell transplantation

Document Type : Original Article

Authors

. Maryam Taghizadeh-Ghehi 1
. Saeed Rezaee 2
. Kheirollah Gholami 3
. Molouk Hadjibabaie 3

1 Research Center for Rational Use of Drugs, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Pharmaceutics, Zanjan University of Medical Sciences, Zanjan, Iran

3 Research Center for Rational Use of Drugs and Clinical Pharmacy Department, Tehran University of Medical Sciences, Tehran, Iran

Abstract
Objective: Many hematopoietic stem cell transplantation (HSCT) patients receive 
vancomycin empirically during febrile neutropenia. There are several models for estimation of 
vancomycin pharmacokinetic parameters and calculation of initial dosing regimen accordingly. 
However, the performance of these methods in HSCT patients remained to be evaluated. 
The aim of the study was to determine which of the vancomycin population pharmacokinetic 
methods best fit Iranian HSCT patients.
Methods: In order to evaluate predicted performance of seven vancomycin population 
pharmacokinetic models, the pharmacokinetic parameters of patients were estimated using 
each model’s equations. Then the predicted steady‑state trough vancomycin concentration was 
calculated based on each model’s parameters and using a formula based on Sawchuk–Zaske 
method. The predicted steady‑state trough vancomycin concentration and the real measured 
concentrations were compared to see which method was the most precise and least biased 
using mean squared error (MSE) and mean prediction error (ME) respectively.
Findings: Forty‑six patients (65% men) were included in the study. Calculated metrics showed 
a range of 38% under‑prediction bias with Rodvold to 34% over‑prediction bias with Matzke and 
Burton models. Birt and revised Burton methods showed no significant bias(ME [95% confidence 
interval(CI)]: –0.067 [–0.235–0.101] and 0.066 [–0.105–0.238]). Birt and revised Burton were not 
different significantly considering MSE (95% CI) of 0.385 (0.227–0.544) and 0.401 (0.255–0.546), 
respectively. Comparisons of precision with naive predictors revealed a delta MSE (95% CI) 
of –0.128 (–1.379–1.890) for Birt and 0.026 (–0.596–0.940) for revised Burton models.
Conclusion: Although the Birt and Burton revised methods performed well, none of the 
studied models showed acceptable performance to be implemented as a routine method 
for initial dose calculation in HSCT patients. A vancomycin pharmacokinetic model specific 
for this high‑risk subpopulation of Iranian patients should be designed and validated.

Keywords

Hematopoietic stem cell transplantation
population pharmacokinetics
  predictive performance
Vancomycin
1. Paul M, Borok S, Fraser A, Vidal L, Leibovici L. Empirical 
antibiotics against Gram‑positive infections for febrile 
neutropenia: Systematic review and meta‑analysis of 
randomized controlled trials. J Antimicrob Chemother 
2005;55:436‑44.
2. de Naurois J, Novitzky‑Basso I, Gill MJ, Marti FM, Cullen MH, 
RoilaF, et al. Management of febrile neutropenia: ESMO Clinical 
Practice Guidelines. Ann Oncol 2010;21 Suppl 5:v252‑6.
3. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, 
Mullen CA, et al. Clinical practice guideline for the use of 
antimicrobial agents in neutropenic patients with cancer: 
2010 update by the infectious diseases society of America. 
Clin Infect Dis 2011;52:e56‑93.
4. Jarkowski A 3rd, Forrest A, Sweeney RP, Tan W, Segal BH, 
Almyroudis N, et al. Characterization of vancomycin 
pharmacokinetics in the adult acute myeloid leukemia 
population. J Oncol Pharm Pract 2012;18:91‑6.
5. Al‑Kofide H, Zaghloul I, Al‑Naim L. Pharmacokinetics of 
vancomycin in adult cancer patients. J Oncol Pharm Pract 
2010;16:245‑50.
6. Teramachi H, Matsushita R, Tsuji A. Influence of malignancy 
on the pharmacokinetics of vancomycin hydrochloride in 
Japanese MRSA patients after dosage adjustment with the 
Bayesian method. Jpn J Chemother 2005;53:357‑63.
7. Lee E, Winter ME, Boro MS. Comparing two predictive 
methods for determining serum vancomycin concentrations 
at a Veterans Affairs Medical Center. Am J Health Syst Pharm 
2006;63:1872‑5.
8. Lake KD, Peterson CD. A simplified dosing method for 
initiating vancomycin therapy. Pharmacotherapy 1985;5:340‑4.
9. Elshaug EK, Manning L, Rawlins MD, Ridley BL, Ingram PR. 
Potential utility for nomogram‑based vancomycin dosing. Int 
J Infect Dis 2013;17:e355‑6.
10. Birt JK, Chandler MH. Using clinical data to determine 
vancomycin dosing parameters. Ther Drug Monit 
1990;12:206‑9.
11. Buelga DS, del Mar Fernandez de Gatta M, Herrera EV, 
Dominguez‑Gil A, García MJ. Population pharmacokinetic 
analysis of vancomycin in patients with hematological 
malignancies. Antimicrob Agents Chemother 2005;49:4934‑41.
12. Ghehi MT, Rezaee S, Hayatshahi A, Hadjibabaie M, 
Gholami K, Javadi M, et al. Vancomycin Pharmacokinetic Parameters in Patients Undergoing Hematopoietic Stem Cell 
Transplantation (HSCT). Int J Hematol Oncol Stem Cell Res 
2013;7:1‑9.
13. Lortholary O, Lefort A, Tod M, Chomat AM, Darras‑Joly C, 
Cordonnier C, et al. Pharmacodynamics and pharmacokinetics 
of antibacterial drugs in the management of febrile neutropenia. 
Lancet Infect Dis 2008;8:612‑20.
14. Omote S, Yano Y, Hashida T, Masuda S, Yano I, Katsura T, et al. 
A retrospective analysis of vancomycin pharmacokinetics in 
Japanese cancer and non‑cancer patients based on routine 
trough monitoring data. Biol Pharm Bull 2009;32:99‑104.
15. Le Normand Y, Milpied N, Kergueris MF, Harousseau JL. 
Pharmacokinetic parameters of vancomycin for therapeutic 
regimens in neutropenic adult patients. Int J Biomed Comput 
1994;36:121‑5.
16. Murphy JE, Gillespie DE, Bateman CV. Predictability of 
vancomycin trough concentrations using seven approaches 
for estimating pharmacokinetic parameters. Am J Health Syst 
Pharm 2006;63:2365‑70.
17. Matzke GR, McGory RW, Halstenson CE, Keane WF. 
Pharmacokinetics of vancomycin in patients with various 
degrees of renal function. Antimicrob Agents Chemother 
1984;25:433‑7.
18. Burton ME, Gentle DL, Vasko MR. Evaluation of a Bayesian 
method for predicting vancomycin dosing. Ann Pharmacother 
1989;23:294‑300.
19. Rodvold KA, Blum RA, FischerJH, Zokufa HZ, RotschaferJC, 
Crossley KB, et al. Vancomycin pharmacokinetics in patients 
with various degrees of renal function. Antimicrob Agents 
Chemother 1988;32:848‑52.
20. Sánchez JL, Dominguez AR, Lane JR, Anderson PO, 
CapparelliEV, Cornejo‑BravoJM. Population pharmacokinetics 
of vancomycin in adult and geriatric patients: Comparison of 
eleven approaches. Int J Clin Pharmacol Ther 2010;48:525‑33.
21. Ambrose PJ, Winter ME. Vancomycin. In: Winter ME, editor. 
Basic Clinical Pharmacokinetics. 4th ed. Philadelphia: Wolters 
Kluwer/Lippincott Williams and Wilkins; 2004. p. 451‑76.
22. Rushing TA, Ambrose PJ. Clinical application and evaluation 
of vancomycin dosing in adults. J Pharm Technol 2001;17:33‑8.
23. Bauer L. Applied Clinical Pharmacokinetics. 2nd ed. New York: 
McGraw‑Hill; 2008.
24. Cockcroft DW, Gault MH. Prediction of creatinine clearance 
from serum creatinine. Nephron 1976;16:31‑41.
25. Salazar DE, Corcoran GB. Predicting creatinine clearance and 
renal drug clearance in obese patients from estimated fat‑free 
body mass. Am J Med 1988;84:1053‑60.
26. McCarron MM, Devine BJ. Clinical pharmacy: Case studies 
case number 25 gentamicin therapy. Ann Pharmacother 
1974;8:650‑5.
27. SheinerLB, Beal SL. Some suggestions for measuring predictive 
performance. J Pharmacokinet Biopharm 1981;9:503‑12.
28. MarsotA, BoulameryA, Bruguerolle B, Simon N. Vancomycin: 
A review of population pharmacokinetic analyses. Clin 
Pharmacokinet 2012;51:1‑13
Journal of Research in Pharmacy Practice
Volume 4, Issue 3
Summer 2015
Pages 129-134

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