Pharmacokinetic outcomes of a simplified, weight-based, extended-interval gentamicin dosing protocol in critically ill neonates.
OBJECTIVE
To determine the pharmacokinetic outcomes of a simplified, weight-based, extended-interval gentamicin dosing protocol for critically ill neonates.


METHODS
Retrospective medical record review with pharmacokinetic analysis.


METHODS
Two neonatal intensive care units in a pediatric tertiary care system.


METHODS
Sequential sample of 644 critically ill neonates less than 7 days old without evidence of renal dysfunction who received gentamicin, dosed by using a simplified, weight-based, extended-interval dosing protocol, on the first day of life for suspected sepsis between February 2003 and January 2008, and who had subsequent gentamicin plasma concentrations measured during their first week of life.


RESULTS
Data were collected on birth weight, gestational age at birth, serum creatinine concentration during the first 10 days of life, medical conditions, and concomitant drugs. Gentamicin dosing and its pharmacokinetic parameters were noted for each patient. A mean dose of 3.96 mg/kg/dose of gentamicin was administered intravenously every 48 hours in neonates weighing less than 1250 g at birth and every 24 hours in those weighing 1250 g or more. If the neonate received concurrent indomethacin, however, gentamicin was given every 48 hours. Protocol success was defined as a peak gentamicin plasma concentration of 7-10 mg/L and a trough concentration less than 2 mg/L. Mean gentamicin peak and trough concentrations were 9.38 mg/L (95% confidence interval [CI] 9.24-9.52 mg/L) and 1.00 mg/L (95% CI 0.96-1.04 mg/L), respectively. With use of the protocol, 361 neonates (56.1%) achieved gentamicin peak plasma concentrations in the range defined as successful and 610 neonates (94.7%) achieved successful trough concentrations. The mean gentamicin apparent volume of distribution and half-life were 0.48 L/kg (95% CI 0.47-0.49 L/kg) and 8.31 hours (95% CI 8.09-8.52 hrs), respectively.


CONCLUSIONS
This simplified, weight-based, extended-interval gentamicin dosing protocol for critically ill neonates was effective in achieving therapeutic peak plasma concentrations of gentamicin in most of the patients and, as a high proportion of patients had acceptable trough concentrations, may minimize the potential for toxicity.
Hoff
David S
DS
Department of Pharmacy, Children's Hospitals and Clinics of Minnesota, Minneapolis, MN 55404, USA. david.hoff@childrensmn.org
Wilcox
Roger A
RA
Tollefson
Lisa M
LM
Lipnik
Polina G
PG
Commers
Amy R
AR
Liu
Meixia
M
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001724:Birth Weight; D016638:Critical Illness; D004334:Drug Administration Schedule; D005839:Gentamicins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005865:Gestational Age; D006207:Half-Life; D006801:Humans; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal; D012189:Retrospective Studies; D014481:United States
D000900:Anti-Bacterial Agents; D005839:Gentamicins