Article date: January 2005
By: M. Lingvall, D. Reith, R. Broadbent, in Volume 59, Issue 1, pages 54-61
Aim
To investigate the effect of sepsis upon the volume of distribution (Vd) of gentamicin in neonates.
Methods
A retrospective chart review was conducted of neonates admitted to Dunedin Hospital who had gentamicin concentrations performed between 1st January 2000 and 30th October 2003. Data from 277 neonates, including a total of 576 gentamicin concentrations, were included in the pharmacokinetic analysis. Fifteen (5.4%) of the neonates had confirmed sepsis. Pharmacokinetic analyses were performed with NONMEM using a one compartment first order elimination model. Duration of infusion (D) was included as a parameter in the model. Covariates included sepsis (SEP), chronological age, gestational age (GA), birth weight, current weight, gender, Apgar score at 1 (AP1) and 5 (AP2) minutes, plasma C‐reactive protein and serum creatinine.
Results
The initial model provided a mean estimates of clearance (CL) of 0.0460 l kg−1 h−1, volume of distribution (Vd) of 0.483 l kg−1 and D of 0.748 h. The magnitudes of interpatient variability, expressed as CV%, were 29.2% for CL, 20.8% for Vd and 71.5% for D. The magnitude of residual variability in gentamicin concentrations was 88.0%. The final pharmacokinetic model was: CL = (0.0177 + 0.00147 • (GA‐20) + 0.000635 • AP2) l kg−1 h−1, Vd = (0.483 +0.0656 • sepsis) l kg−1, D = 0.672 h. The interpatient variability (CV%) was 22.8% for CL, 22.8% for Vd and 97.7% for D. The magnitude of residual variability in gentamicin concentrations was 83.3%.
Conclusions
The 14% increase in Vd in septic neonates implies that larger doses may be required to achieve peak therapeutic concentrations in the presence of sepsis. D is an important parameter in neonatal pharmacokinetic models.
DOI: 10.1111/j.1365-2125.2005.02260.x
View this article