Skip to main content
SpringerLink
Log in

Amikacin Maturation Model as a Marker of Renal Maturation to Predict Glomerular Filtration Rate and Vancomycin Clearance in Neonates

  • Short Communication
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Abstract

Background and Objective

Amikacin clearance has recently been proposed as a marker of renal maturation in neonates. However, the predictive value of this marker is still unknown. The objective of the present exploratory study was to evaluate the predictive performance of renal maturation model derived from amikacin to predict the glomerular filtration rate (GFR) and vancomycin clearance in neonates.

Methods

The GFR and vancomycin clearance in neonates were predicted using a maturation model derived from amikacin via estimation and simulation in a cohort of 116 neonates using non-linear mixed–effects modeling NONMEM® software.

Results

Our results demonstrate good correlations between predicted and observed GFR and vancomycin clearance in neonates. The square of the correlation coefficient, and means of the prediction error (2.5th–97.5th percentiles) and absolute prediction error (2.5th–97.5th percentiles) are 0.96, 1.2 % (−39.7 to 30.0 %) and 12.3 % (0.4–39.7 %), respectively, for GFR, and 0.97, −11.3 % (−38.2 to 15.4 %) and 14.0 % (0.5–38.2 %), respectively, for vancomycin. The prediction error is not significantly correlated with age.

Conclusion

An amikacin maturation model can precisely reflect maturation of glomerular filtration and thus predict the dosage regimens of other renally excreted drugs by glomerular filtration in neonates.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

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

    Article  PubMed  CAS  Google Scholar 

  2. van den Anker JN, Schwab M, Kearns GL. Developmental pharmacokinetics. Handb Exp Pharmacol. 2011;205:51–75.

    Article  PubMed  Google Scholar 

  3. Solhaug MJ, Bolger PM, Jose PA. The developing kidney and environmental toxins. Pediatrics. 2004;113(4(S)):1084–91.

    PubMed  Google Scholar 

  4. Chen N, Aleksa K, Woodland C, et al. Ontogeny of drug elimination by the human kidney. Pediatr Nephrol. 2006;21(2):160–8.

    Article  PubMed  Google Scholar 

  5. Jacqz-Aigrain E, Zhao W, Sharland M, et al. Use of antibacterial agents in the neonate: 50 years of experience with vancomycin administration. Semin Fetal Neonatal Med. 2013;18(1):28–34.

    Article  PubMed  Google Scholar 

  6. Kearns GL, Abdel-Rahman SM, Alander SW, et al. Developmental pharmacology—drug disposition, action, and therapy in infants and children. N Engl J Med. 2003;349(12):1157–67.

    Article  PubMed  CAS  Google Scholar 

  7. Rhodin MM, Anderson BJ, Peters AM, et al. Human renal function maturation: a quantitative description using weight and postmenstrual age. Pediatr Nephrol. 2009;24(1):67–76.

    Article  PubMed  Google Scholar 

  8. Allegaert K, Anderson BJ, van den Anker JN, et al. Renal drug clearance in preterm neonates: relation to prenatal growth. Ther Drug Monit. 2007;29(3):284–91.

    Article  PubMed  CAS  Google Scholar 

  9. 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(1):75–84.

    Article  PubMed  CAS  Google Scholar 

  10. Koren G, James A, Perlman M. A simple method for the estimation of glomerular filtration rate by gentamicin pharmacokinetics during routine drug monitoring in the newborn. Clin Pharmacol Ther. 1985;38(6):680–5.

    Article  PubMed  CAS  Google Scholar 

  11. De Cock RF, Allegaert K, Schreuder MF, et al. Maturation of the glomerular filtration rate in neonates, as reflected by amikacin clearance. Clin Pharmacokinet. 2012;51(2):105–17.

    Article  PubMed  Google Scholar 

  12. Pacifici GM. Clinical pharmacokinetics of aminoglycosides in the neonate: a review. Eur J Clin Pharmacol. 2009;65(4):419–27.

    Article  PubMed  CAS  Google Scholar 

  13. Panomvana D, Kiatjaroensin SA, Phiboonbanakit D. Correlation of the pharmacokinetic parameters of amikacin and ceftazidime. Clin Pharmacokinet. 2007;46(10):859–66.

    Article  PubMed  CAS  Google Scholar 

  14. Bleyzac N, Varnier V, Labaune JM, et al. Population pharmacokinetics of amikacin at birth and interindividual variability in renal maturation. Eur J Clin Pharmacol. 2001;57(6–7):499–504.

    PubMed  CAS  Google Scholar 

  15. Tréluyer JM, Merlé Y, Tonnelier S, et al. Nonparametric population pharmacokinetic analysis of amikacin in neonates, infants, and children. Antimicrob Agents Chemother. 2002;46(5):1381–7.

    Article  PubMed  Google Scholar 

  16. McNamara PJ, Alcorn J. Protein binding predictions in infants. AAPS PharmSci. 2002;4(1):E4.

    Article  PubMed  Google Scholar 

  17. Johnson TN, Rostami-Hodjegan A, Tucker GT. Prediction of the clearance of eleven drugs and associated variability in neonates, infants and children. Clin Pharmacokinet. 2006;45(9):931–56.

    Article  PubMed  CAS  Google Scholar 

  18. Zhao W, Lopez E, Biran V, et al. Vancomycin continuous infusion in neonates: dosing optimisation and therapeutic drug monitoring. Arch Dis Child. 2013;98(6):449–53.

    Article  PubMed  Google Scholar 

  19. Knudsen JD, Fuursted K, Espersen F, et al. Activities of vancomycin and teicoplanin against penicillin-resistant pneumococci in vitro and in vivo and correlation to pharmacokinetic parameters in the mouse peritonitis model. Antimicrob Agents Chemother. 1997;41(9):1910–5.

    PubMed  CAS  Google Scholar 

  20. Delattre IK, Musuamba FT, Verbeeck RK, et al. Empirical models for dosage optimization of four beta-lactams in critically ill septic patients based on therapeutic drug monitoring of amikacin. Clin Biochem. 2010;43(6):589–98.

    Article  PubMed  CAS  Google Scholar 

  21. Hooker AC, Staatz CE, Karlsson MO. Conditional weighted residuals (CWRES): a model diagnostic for the FOCE method. Pharm Res. 2007;24:2187–97.

    Article  PubMed  CAS  Google Scholar 

  22. Brendel K, Comets E, Laffont C, et al. Metrics for external model evaluation with an application to the population pharmacokinetics of gliclazide. Pharm Res. 2006;23(9):2036–49.

    Article  PubMed  CAS  Google Scholar 

  23. Comets E, Brendel K, Mentré F. Computing normalised prediction distribution errors to evaluate nonlinear mixed-effect models: the npde add-on package for R. Comput Methods Programs Biomed. 2008;90(2):154–66.

    Article  PubMed  Google Scholar 

  24. Cella M, Knibbe C, Danhof M, et al. What is the right dose for children? Br J Clin Pharmacol. 2010;70(4):597–603.

    Article  PubMed  CAS  Google Scholar 

  25. Cella M, Gorter de Vries F, Burger D, et al. A model-based approach to dose selection in early pediatric development. Clin Pharmacol Ther. 2010;87(3):294–302.

    Article  PubMed  CAS  Google Scholar 

  26. Johnson TN. The problems in scaling adult drug doses to children. Arch Dis Child. 2008;93(3):207–11.

    Article  PubMed  CAS  Google Scholar 

  27. Barrett JS, Della Casa Alberighi O, Läer S, et al. Physiologically based pharmacokinetic (PBPK) modeling in children. Clin Pharmacol Ther. 2012;92(1):40–9.

    Article  PubMed  CAS  Google Scholar 

  28. Edginton AN, Schmitt W, Willmann S. Development and evaluation of a generic physiologically based pharmacokinetic model for children. Clin Pharmacokinet. 2006;45(10):1013–34.

    Article  PubMed  CAS  Google Scholar 

  29. Golper TA, Noonan HM, Elzinga L, et al. Vancomycin pharmacokinetics, renal handling, and nonrenal clearances in normal human subjects. Clin Pharmacol Ther. 1988;43(5):565–70.

    Article  PubMed  CAS  Google Scholar 

  30. Traynor J, Mactier R, Geddes CC, et al. How to measure renal function in clinical practice. BMJ. 2006;333(7571):733–7.

    Article  PubMed  Google Scholar 

  31. Swinkels DW, Hendriks JC, Nauta J, et al. Glomerular filtration rate by single-injection inulin clearance: definition of a workable protocol for children. Ann Clin Biochem. 2000;37(1):60–6.

    Article  PubMed  CAS  Google Scholar 

  32. van Rossum LK, Cransberg K, de Rijke YB, et al. Determination of inulin clearance by single injection or infusion in children. Pediatr Nephrol. 2005;20(6):777–81.

    Article  PubMed  Google Scholar 

  33. Bird NJ, Henderson BL, Lui D, et al. Indexing glomerular filtration rate to suit children. J Nucl Med. 2003;44(7):1037–43.

    PubMed  Google Scholar 

  34. Stake G, Monclair T. A single plasma sample method for estimation of the glomerular filtration rate in infants and children using iohexol, I: establishment of a body weight-related formula for the distribution volume of iohexol. Scand J Clin Lab Invest. 1991;51(4):335–42.

    Article  PubMed  CAS  Google Scholar 

  35. Blake GM, Gardiner N, Gnanasegaran G, et al. Reference ranges for 51Cr-EDTA measurements of glomerular filtration rate in children. Nucl Med Commun. 2005;26(11):983–7.

    Article  PubMed  Google Scholar 

  36. Gutte H, Møller ML, Pfeifer AK, et al. Estimating GFR in children with 99mTc-DTPA renography: a comparison with single-sample 51Cr-EDTA clearance. Clin Physiol Funct Imaging. 2010;30(3):169–74.

    Article  PubMed  CAS  Google Scholar 

  37. Peake M, Whiting M. Measurement of serum creatinine—current status and future goals. Clin Biochem Rev. 2006;27(4):173–84.

    PubMed  Google Scholar 

  38. van den Anker JN. Renal function in preterm infants. Eur J Pediatr. 1997;156(7):583–4.

    PubMed  Google Scholar 

  39. Zhao W, Kaguelidou F, Biran V, et al. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings. Br J Clin Pharmacol. 2013;75(4):1068–80.

    Article  CAS  Google Scholar 

  40. Delattre IK, Musuamba FT, Jacqmin P, et al. Population pharmacokinetics of four β-lactams in critically ill septic patients comedicated with amikacin. Clin Biochem. 2012;45(10–11):780–6.

    Article  PubMed  CAS  Google Scholar 

  41. Seay RE, Brundage RC, Jensen PD, et al. Population pharmacokinetics of vancomycin in neonates. Clin Pharmacol Ther. 1994;56(2):169–75.

    Article  PubMed  CAS  Google Scholar 

  42. Allegaert K, Cossey V, Debeer A, et al. The impact of ibuprofen on renal clearance in preterm infants is independent of the gestational age. Pediatr Nephrol. 2005;20(6):740–3.

    Article  PubMed  Google Scholar 

  43. Schreuder MF, Wilhelm AJ, Bökenkamp A, et al. Impact of gestational age and birth weight on amikacin clearance on day 1 of life. Clin J Am Soc Nephrol. 2009;4(11):1774–8.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by “la Foundation PremUp” (Professor Danièle Evain Brion, France) and Global Research in Paediatrics—Network of Excellence (GRIP, EU-funded FP7 project, Grant Agreement number 261060).

The authors declare no conflict of interest related to this work.

Author information

Authors and Affiliations

  1. Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, APHP, Clinical Investigation Center CIC9202, INSERM, 48 Boulevard Sérurier, 75935, Paris Cedex 19, France

    Wei Zhao & Evelyne Jacqz-Aigrain

  2. Clinical Investigation Center CIC9202, INSERM, Paris, France

    Wei Zhao & Evelyne Jacqz-Aigrain

  3. NICU, Hôpital Robert Debré, Paris, France

    Valérie Biran

  4. Université Paris Diderot, Sorbonne Paris Cité, Paris, France

    Evelyne Jacqz-Aigrain

Authors
  1. Wei Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Valérie Biran
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Evelyne Jacqz-Aigrain
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Wei Zhao or Evelyne Jacqz-Aigrain.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhao, W., Biran, V. & Jacqz-Aigrain, E. Amikacin Maturation Model as a Marker of Renal Maturation to Predict Glomerular Filtration Rate and Vancomycin Clearance in Neonates. Clin Pharmacokinet 52, 1127–1134 (2013). https://doi.org/10.1007/s40262-013-0101-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40262-013-0101-6

Keywords

Search

Navigation