Evaluation of the Effect of Intravenous Volume Expanders upon the Volume of Distribution of Gentamicin in Septic Neonates

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Sepsis has been reported to increase the volume of distribution of gentamicin in neonates. To determine whether this was caused by the use of intravenous volume expanders a retrospective nested case-control study was performed comparing confirmed septic neonates with non-septic controls. Data were collected on intravenous administration of 0.45% saline/10% dextrose, 0.45% saline/5% dextrose, 0.9% normal saline, red blood cells, platelets, immunoglobulin (Intragam P) and albumin. A population pharmacokinetic analysis was performed using NONMEM for 116 neonates (29 confirmed septic) from which 363 gentamicin serum concentrations were available. The final covariate model was CL=0.097x(current weight/2)(1.3)x(postnatal age/7)(0.29) and V=1.07x(current weight/2)(0.8)+(confirmed sepsis)x0.13. The gentamicin volume of distribution was not significantly influenced by the cumulative intravenous volume expanders. The principal covariates that affected the gentamicin volume of distribution were current body weight and confirmed sepsis.



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