Altered gentamicin pharmacokinetics in term neonates undergoing controlled hypothermia.
Br J Clin Pharmacol
; 81(6): 1067-77, 2016 06.
Article
en En
| MEDLINE
| ID: mdl-26763684
ABSTRACT
AIM(S) Little is known about the pharmacokinetic (PK) properties of gentamicin in newborns undergoing controlled hypothermia after suffering from hypoxic−ischaemic encephalopathy due to perinatal asphyxia. This study prospectively evaluates and describes the population PK of gentamicin in these patients METHODS:
Demographic, clinical and laboratory data of patients included in a multicentre prospective observational cohort study (the 'PharmaCool Study') were collected. A non-linear mixed-effects regression analysis (nonmem®) was performed to describe the population PK of gentamicin. The most optimal dosing regimen was evaluated based on simulations of the final model.RESULTS:
A total of 47 patients receiving gentamicin were included in the analysis. The PK were best described by an allometric two compartment model with gestational age (GA) as a covariate on clearance (CL). During hypothermia the CL of a typical patient (3 kg, GA 40 weeks, 2 days post-natal age (PNA)) was 0.06 l kg−1 h−1 (inter-individual variability (IIV) 26.6%) and volume of distribution of the central compartment (Vc) was 0.46 l kg−1 (IIV 40.8%). CL was constant during hypothermia and rewarming, but increased by 29% after reaching normothermia (>96 h PNA).CONCLUSIONS:
This study describes the PK of gentamicin in neonates undergoing controlled hypothermia. The 29% higher CL in the normothermic phase compared with the preceding phases suggests a delay in normalization of CL after rewarming has occurred. Based on simulations we recommend an empiric dose of 5 mg kg−1 every 36 h or every 24 h for patients with GA 3640 weeks and GA 42 weeks, respectively.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Gentamicinas
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Hipotermia Inducida
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Antibacterianos
Tipo de estudio:
Clinical_trials
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Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Female
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Humans
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Male
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Newborn
Idioma:
En
Revista:
Br J Clin Pharmacol
Año:
2016
Tipo del documento:
Article