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. 1999 Nov;81(3):F221–F227. doi: 10.1136/fn.81.3.f221

Pharmacokinetics and dose requirements of vancomycin in neonates

C Grimsley, A Thomson
PMCID: PMC1721000  PMID: 10525029

Abstract

AIMS—To design and evaluate dosing guidelines for vancomycin based on data collected during routine use of the drug.
METHODS—Following the observation that 66% of neonatal vancomycin trough concentrations were outside the target range, new dose guidelines were developed using a population pharmacokinetic approach. NONMEM (non-linear mixed effects model) was used to analyse dose histories and 347 concentration measurements collected during routine therapeutic drug monitoring in 59neonates.
RESULTS—Postconceptual ages in the patient group ranged from 26-45 weeks, weights from 0.57-4.23 kg, and creatinine concentrations from 18-172 µmol/l. The population estimate of vancomycin clearance (l/h/kg) was 3.56/creatinine concentration (µmol/l) with an interpatient coefficient of variation (CV) of 22% and volume of distribution 0.67 l/kg with a CV of 18%. Residual error was 4.5 mg/l. When the new recommendations on dosing were used prospectively in a separate group of neonates the proportion of acceptable troughs increased from 33% to 72%.
CONCLUSIONS—The pharmacokinetics of vancomycin in neonates and young infants depend on weight and serum creatinine. Preliminary results from the new guidelines indicate an improvement on previous practice, but also an ongoing need to monitor concentrations.



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Selected References

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  1. Asbury W. H., Darsey E. H., Rose W. B., Murphy J. E., Buffington D. E., Capers C. C. Vancomycin pharmacokinetics in neonates and infants: a retrospective evaluation. Ann Pharmacother. 1993 Apr;27(4):490–496. doi: 10.1177/106002809302700417. [DOI] [PubMed] [Google Scholar]
  2. Battisti O., Mitchison R., Davies P. A. Changing blood culture isolates in a referral neonatal intensive care unit. Arch Dis Child. 1981 Oct;56(10):775–778. doi: 10.1136/adc.56.10.775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baumgart S., Hall S. E., Campos J. M., Polin R. A. Sepsis with coagulase-negative staphylococci in critically ill newborns. Am J Dis Child. 1983 May;137(5):461–463. doi: 10.1001/archpedi.1983.02140310043012. [DOI] [PubMed] [Google Scholar]
  4. Fernández de Gatta M. D., Calvo M. V., Hernández J. M., Caballero D., San Miguel J. F., Domínguez-Gil A. Cost-effectiveness analysis of serum vancomycin concentration monitoring in patients with hematologic malignancies. Clin Pharmacol Ther. 1996 Sep;60(3):332–340. doi: 10.1016/S0009-9236(96)90060-0. [DOI] [PubMed] [Google Scholar]
  5. Gabriel M. H., Kildoo G. C., 3rd, Gennrich J. L., Modanlou H. D., Collins S. R. Prospective evaluation of a vancomycin dosage guideline for neonates. Clin Pharm. 1991 Feb;10(2):129–132. [PubMed] [Google Scholar]
  6. James A., Koren G., Milliken J., Soldin S., Prober C. Vancomycin pharmacokinetics and dose recommendations for preterm infants. Antimicrob Agents Chemother. 1987 Jan;31(1):52–54. doi: 10.1128/aac.31.1.52. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jarrett R. V., Marinkovich G. A., Gayle E. L., Bass J. W. Individualized pharmacokinetic profiles to compute vancomycin dosage and dosing interval in preterm infants. Pediatr Infect Dis J. 1993 Feb;12(2):156–157. doi: 10.1097/00006454-199302000-00010. [DOI] [PubMed] [Google Scholar]
  8. Leonard M. B., Koren G., Stevenson D. K., Prober C. G. Vancomycin pharmacokinetics in very low birth weight neonates. Pediatr Infect Dis J. 1989 May;8(5):282–286. [PubMed] [Google Scholar]
  9. Lisby-Sutch S. M., Nahata M. C. Dosage guidelines for the use of vancomycin based on its pharmacokinetics in infants. Eur J Clin Pharmacol. 1988;35(6):637–642. doi: 10.1007/BF00637600. [DOI] [PubMed] [Google Scholar]
  10. McDougal A., Ling E. W., Levine M. Vancomycin pharmacokinetics and dosing in premature neonates. Ther Drug Monit. 1995 Aug;17(4):319–326. doi: 10.1097/00007691-199508000-00001. [DOI] [PubMed] [Google Scholar]
  11. Naqvi S. H., Keenan W. J., Reichley R. M., Fortune K. P. Vancomycin pharmacokinetics in small, seriously ill infants. Am J Dis Child. 1986 Feb;140(2):107–110. doi: 10.1001/archpedi.1986.02140160025021. [DOI] [PubMed] [Google Scholar]
  12. Pryka R. D., Rodvold K. A., Erdman S. M. An updated comparison of drug dosing methods. Part IV: Vancomycin. Clin Pharmacokinet. 1991 Jun;20(6):463–476. doi: 10.2165/00003088-199120060-00003. [DOI] [PubMed] [Google Scholar]
  13. Reed M. D., Kliegman R. M., Weiner J. S., Huang M., Yamashita T. S., Blumer J. L. The clinical pharmacology of vancomycin in seriously ill preterm infants. Pediatr Res. 1987 Sep;22(3):360–363. doi: 10.1203/00006450-198709000-00024. [DOI] [PubMed] [Google Scholar]
  14. Rodvold K. A., Everett J. A., Pryka R. D., Kraus D. M. Pharmacokinetics and administration regimens of vancomycin in neonates, infants and children. Clin Pharmacokinet. 1997 Jul;33(1):32–51. doi: 10.2165/00003088-199733010-00004. [DOI] [PubMed] [Google Scholar]
  15. Rowe P. M. Preparing for battle against vancomycin resistance. Lancet. 1996 Jan 27;347(8996):252–252. doi: 10.1016/s0140-6736(96)90420-1. [DOI] [PubMed] [Google Scholar]
  16. Schaad U. B., McCracken G. H., Jr, Nelson J. D. Clinical pharmacology and efficacy of vancomycin in pediatric patients. J Pediatr. 1980 Jan;96(1):119–126. doi: 10.1016/s0022-3476(80)80347-7. [DOI] [PubMed] [Google Scholar]
  17. Schaible D. H., Rocci M. L., Jr, Alpert G. A., Campos J. M., Paul M. H., Polin R. A., Plotkin S. A. Vancomycin pharmacokinetics in infants: relationships to indices of maturation. Pediatr Infect Dis. 1986 May-Jun;5(3):304–308. doi: 10.1097/00006454-198605000-00006. [DOI] [PubMed] [Google Scholar]
  18. Seay R. E., Brundage R. C., Jensen P. D., Schilling C. G., Edgren B. E. Population pharmacokinetics of vancomycin in neonates. Clin Pharmacol Ther. 1994 Aug;56(2):169–175. doi: 10.1038/clpt.1994.120. [DOI] [PubMed] [Google Scholar]

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