A gentamicin pharmacokinetic population model and once-daily dosing algorithm for neonates.
OBJECTIVE
To develop a gentamicin pharmacokinetic population model and once-daily dosing algorithm for neonates younger than 10 days.


METHODS
Prospective, open-label study.


METHODS
Neonatal intensive care unit.


METHODS
One hundred thirty-nine neonates prescribed gentamicin.


RESULTS
Gentamicin peak and trough serum concentrations were collected from 139 neonates divided into three groups who were receiving one of the following intravenous 24-hour gentamicin regimens during the first 10 days of life, based on gestational age and birth weight (group 1, < 28 wks, 2.5 mg/kg; group 2, 28-34 wks, 3 mg/kg; and group 3, > 34 wks, 4 mg/kg). A structural model was developed in ADAPT II software using a MAP Bayesian approach. Final population parameter estimates were calculated using iterative two-stage analysis. The median (range) gestational age and birth weight, respectively, were 32 weeks (23-42 wks) and 1.92 kg (0.47-5.00 kg). The final one-compartmental linear model had a median (range) gentamicin total clearance, half-life, and volume of distribution of 0.0709 L/hour (0.0151-0.246 L/hr), 8.59 hours (4.88-16.9 hrs), and 0.262 L (0.0903-0.929 L), respectively. Total clearance increased as gestational age increased (p<0.001). Group 1 (10.2 hrs) had a significantly longer half-life than either group 2 (8.89 hrs, p<0.01) or group 3 (6.98 hrs, p<0.01). Total clearance was associated with gestational age and birth weight: clearance (L/hr) = (0.00504 + [0.00108 x gestational age]) x birth weight (coefficient of determination [r2] = 0.897), and volume of distribution was associated with birth weight (r2 = 0.700). The following dosing algorithm was designed to reach a therapeutic 24-hour area under the curve (87.5 mg/L x hr) in neonates during the first 10 days after birth: 24-hour gentamicin dose (mg) = (0.441 + [0.0945 x gestational age]) x birth weight.


CONCLUSIONS
This dosing algorithm provides a new approach for determining initial gentamicin dosing regimens in neonates; however, clinical validation is required.
Department of Pharmacy, Golisano Children's Hospital at Strong, University of Rochester Medical Center, New York 14642, USA. robert_dicenzo@urmc.rochester.edu
Robert
R
DiCenzo
Alan
A
Forrest
Judianne C
JC
Slish
Carol
C
Cole
Ronnie
R
Guillet
D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001499:Bayes Theorem; D001724:Birth Weight; D004334:Drug Administration Schedule; D005839:Gentamicins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D016014:Linear Models; D008954:Models, Biological; D011446:Prospective Studies; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism
D000900:Anti-Bacterial Agents; D005839:Gentamicins