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The effect of sepsis upon gentamicin pharmacokinetics in neonates
Author(s) -
Lingvall M.,
Reith D.,
Broadbent R.
Publication year - 2005
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2005.02260.x
Subject(s) - pharmacokinetics , volume of distribution , gentamicin , medicine , sepsis , gestational age , neonatal sepsis , dose , birth weight , apgar score , creatinine , antibiotics , anesthesia , pregnancy , biology , microbiology and biotechnology , genetics
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.