Two nomograms for determining extended-dosing intervals for gentamicin in neonates.
OBJECTIVE
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 interval for neonates to achieve steady-state trough concentrations of < or =0.5 or < 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 < or =0.5 or < 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.


CONCLUSIONS
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.
Murphy
John E
JE
College of Pharmacy, University of Arizona, Tucson, AZ 85721-0202, USA. murphy@pharmacy.arizona.edu <murphy@pharmacy.arizona.edu>
Roether
Anthony M
AM
D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D005839:Gentamicins / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D007231:Infant, Newborn; D049451:Nomograms
D000900:Anti-Bacterial Agents; D005839:Gentamicins