Population pharmacokinetic models

Effect of explicit versus assumed constant serum concentration assay error patterns upon parameter values of gentamicin in infants on and off extracorporeal membrane oxygenation

W. F. Dodge, R. W. Jelliffe, J. B. Zwischenberger, R. A. Bellanger, J. A. Hokanson, W. R. Snodgrass

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Prior authors had hypothesized (but not clearly found) an increased apparent volume of distribution (V(d)) for gentamicin in neonates undergoing extracorporeal membrane oxygenation (ECMO). We chose to study the question in our own clinical setting. To develop population pharmacokinetic models of the drug, we used the nonparametric expectation and maximization population modeling method and data from 11 neonates who received gentamicin on ECMO, including 6 infants who received gentamicin both on and off ECMO for severe respiratory failure. We found an increased Vd for gentamicin on ECMO and attributed much of the difference from prior investigations to our use of an explicitly determined laboratory assay error pattern for the measured serum concentrations rather than using constant weighting of the serum level data points. For six infants, while on ECMO their median V(d) was 0.748 L/kg compared with a median V(d) of 0.471 L/kg after ECMO was discontinued. The median clearance of gentamicin in the six infants while undergoing ECMO was 0.239 L/h compared with 0.350 L/h after ECMO was discontinued. The median half-time (T( 1/2 )) was 9.24 h while on ECMO compared with 3.87 h when off ECMO. We conclude that while undergoing ECMO, neonates have a higher volume of distribution for gentamicin, a lower clearance, and a much longer half- life. Based on these results, for attainment of the desired peak-and-trough plasma gentamicin concentrations for infants undergoing ECMO (i.e., 5-8 and <2.0 μg/ml, respectively), we now recommend a loading dose of ~4.3 mg/kg of gentamicin and a maintenance dose of ~3.7 mg/kg to be given at dosing intervals of 18-24 h, followed by monitoring of serum concentrations and appropriate dose adjustments thereafter. To attain alternative goals, the model provides different loading and maintenance doses.

Original languageEnglish (US)
Pages (from-to)552-559
Number of pages8
JournalTherapeutic Drug Monitoring
Volume16
Issue number6
StatePublished - 1994

Fingerprint

Extracorporeal Membrane Oxygenation
Pharmacokinetics
Oxygenation
Gentamicins
Assays
Membranes
Serum
Population
Newborn Infant
Respiratory Insufficiency
Half-Life

Keywords

  • Extracorporeal membrane oxygenation
  • Gentamicin
  • Laboratory error assay pattern
  • Population models
  • Term infants

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Health, Toxicology and Mutagenesis
  • Pharmacology (medical)
  • Public Health, Environmental and Occupational Health
  • Pharmacology
  • Toxicology

Cite this

Population pharmacokinetic models : Effect of explicit versus assumed constant serum concentration assay error patterns upon parameter values of gentamicin in infants on and off extracorporeal membrane oxygenation. / Dodge, W. F.; Jelliffe, R. W.; Zwischenberger, J. B.; Bellanger, R. A.; Hokanson, J. A.; Snodgrass, W. R.

In: Therapeutic Drug Monitoring, Vol. 16, No. 6, 1994, p. 552-559.

Research output: Contribution to journalArticle

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