The effect of sepsis upon gentamicin pharmacokinetics in neonates.
Br J Clin Pharmacol
; 59(1): 54-61, 2005 Jan.
Article
em En
| MEDLINE
| ID: mdl-15606440
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções Bacterianas
/
Gentamicinas
/
Sepse
/
Antibacterianos
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Female
/
Humans
/
Male
/
Newborn
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article