Two nomograms for determining extended-dosing intervals for gentamicin in neonates

John E Murphy, Anthony M. Roether

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Purpose. The development of two nomograms to predict dosing intervals for gentamicin in neonates based on one gentamicin concentration is described. Methods. Pooled data from three retrospective studies on neonates age seven days or younger were used to create nomograms that would predict dosing intervals for gentamicin. The population volume of distribution (0.45 L/kg) and a determined half-life were used to create nomogram cutoff concentrations that could select a dosing inter-val for neonates to achieve steady-state trough concentrations of ≤0.5 or ≤1 mg/L. A dose of 4 mg/kg was used to simulate concentration-versus-time profiles for included neonates based on their individual pharmacokinetic data. Predicted concentrations from hours 6 to 22, at one-hour intervals, for each neonate were compared against the nomograms and evaluated for the number of correct interval predictions. The nomograms were considered to have failed at any time point where they indicated an interval that would not have achieved the desired trough concentration of ≤0.5 or ≤1 mg/L or if the interval chosen was longer than necessary. Results. The 0.5- and 1-mg/L nomograms predicted correct dosing intervals for 81-92% of neonates for postinfusion hours between 15 to 21 and 86-93% for postinfusion hours of 13 and 21, respectively. Accuracy of the nomograms to predict correct dosing intervals improved as the postinfusion time before the next concentration measurement increased. Conclusion. Using the two nomograms may help predict the correct extended-dosing intervals of gentamicin administration for neonates. Prospective evaluation and validation of the nomograms may be necessary for their wider use as a clinical tool.

Original languageEnglish (US)
Pages (from-to)624-630
Number of pages7
JournalAmerican Journal of Health-System Pharmacy
Volume65
Issue number7
DOIs
StatePublished - Apr 1 2008

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Nomograms
Gentamicins
Half-Life
Retrospective Studies
Pharmacokinetics
Demography

Keywords

  • Aminoglycosides
  • Blood levels
  • Dosage
  • Drugs, body distribution
  • Gentamicin
  • Half-life
  • Injections
  • Methodology
  • Nomograms
  • Pediatrics
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Leadership and Management

Cite this

Two nomograms for determining extended-dosing intervals for gentamicin in neonates. / Murphy, John E; Roether, Anthony M.

In: American Journal of Health-System Pharmacy, Vol. 65, No. 7, 01.04.2008, p. 624-630.

Research output: Contribution to journalArticle

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abstract = "Purpose. The development of two nomograms to predict dosing intervals for gentamicin in neonates based on one gentamicin concentration is described. Methods. Pooled data from three retrospective studies on neonates age seven days or younger were used to create nomograms that would predict dosing intervals for gentamicin. The population volume of distribution (0.45 L/kg) and a determined half-life were used to create nomogram cutoff concentrations that could select a dosing inter-val for neonates to achieve steady-state trough concentrations of ≤0.5 or ≤1 mg/L. A dose of 4 mg/kg was used to simulate concentration-versus-time profiles for included neonates based on their individual pharmacokinetic data. Predicted concentrations from hours 6 to 22, at one-hour intervals, for each neonate were compared against the nomograms and evaluated for the number of correct interval predictions. The nomograms were considered to have failed at any time point where they indicated an interval that would not have achieved the desired trough concentration of ≤0.5 or ≤1 mg/L or if the interval chosen was longer than necessary. Results. The 0.5- and 1-mg/L nomograms predicted correct dosing intervals for 81-92{\%} of neonates for postinfusion hours between 15 to 21 and 86-93{\%} for postinfusion hours of 13 and 21, respectively. Accuracy of the nomograms to predict correct dosing intervals improved as the postinfusion time before the next concentration measurement increased. Conclusion. Using the two nomograms may help predict the correct extended-dosing intervals of gentamicin administration for neonates. Prospective evaluation and validation of the nomograms may be necessary for their wider use as a clinical tool.",
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AB - Purpose. The development of two nomograms to predict dosing intervals for gentamicin in neonates based on one gentamicin concentration is described. Methods. Pooled data from three retrospective studies on neonates age seven days or younger were used to create nomograms that would predict dosing intervals for gentamicin. The population volume of distribution (0.45 L/kg) and a determined half-life were used to create nomogram cutoff concentrations that could select a dosing inter-val for neonates to achieve steady-state trough concentrations of ≤0.5 or ≤1 mg/L. A dose of 4 mg/kg was used to simulate concentration-versus-time profiles for included neonates based on their individual pharmacokinetic data. Predicted concentrations from hours 6 to 22, at one-hour intervals, for each neonate were compared against the nomograms and evaluated for the number of correct interval predictions. The nomograms were considered to have failed at any time point where they indicated an interval that would not have achieved the desired trough concentration of ≤0.5 or ≤1 mg/L or if the interval chosen was longer than necessary. Results. The 0.5- and 1-mg/L nomograms predicted correct dosing intervals for 81-92% of neonates for postinfusion hours between 15 to 21 and 86-93% for postinfusion hours of 13 and 21, respectively. Accuracy of the nomograms to predict correct dosing intervals improved as the postinfusion time before the next concentration measurement increased. Conclusion. Using the two nomograms may help predict the correct extended-dosing intervals of gentamicin administration for neonates. Prospective evaluation and validation of the nomograms may be necessary for their wider use as a clinical tool.

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