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The effect of sepsis upon gentamicin pharmacokinetics in neonates

Lingvall, M. ; Reith, D. ; Broadbent, R.

British Journal of Clinical Pharmacology, January 2005, Vol.59(1), pp.54-61 [Tạp chí có phản biện]

ISSN: 0306-5251 ; E-ISSN: 1365-2125 ; DOI: 10.1111/j.1365-2125.2005.02260.x

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  • Nhan đề:
    The effect of sepsis upon gentamicin pharmacokinetics in neonates
  • Tác giả: Lingvall, M. ; Reith, D. ; Broadbent, R.
  • Chủ đề: Apgar ; Gentamicin ; Neonate ; Pharmacokinetics ; Sepsis
  • Là 1 phần của: British Journal of Clinical Pharmacology, January 2005, Vol.59(1), pp.54-61
  • Mô tả: 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 super(-1) h super(-1), volume of distribution (Vd) of 0.483 l kg super(-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 times (GA-20) + 0.000635 times AP2) l kg super(-1) h super(-1), Vd = (0.483 +0.0656 times sepsis) l kg super(-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.
  • Số nhận dạng: ISSN: 0306-5251 ; E-ISSN: 1365-2125 ; DOI: 10.1111/j.1365-2125.2005.02260.x

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