A gentamicin pharmacokinetic population model and once-daily dosing algorithm for neonates

Study Objective. To develop a gentamicin pharmacokinetic population model and once-daily dosing algorithm for neonates younger than 10 days. Design. Prospective, open-label study. Setting. Neonatal intensive care unit. Patients. One hundred thirty-nine neonates prescribed gentamicin. Measurements and Main 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 . gestational age]) . birth weight (coefficient of determination [r(2)] = 0.897), and volume of distribution was associated with birth weight (r(2) = 0.700). The following dosing algorithm was designed to reach a therapeutic 24-hour area under the curve (87.5 mg/L.hr) in neonates during the first 10 days after birth: 24-hour gentamicin dose (mg) = (0.441 + [0.0945 . gestational age]) . birth weight. Conclusion. This dosing algorithm. provides a new approach for determining initial gentamicin dosing regimens in neonates; however, clinical validation is required.