Background and aim Cefazolin (CFZ) is highly and saturably bound to albumin in adults. It is mainly used as prophylactic antibiotic agent. The aim of the present study is to describe CFZ protein binding and its covariates in neonates.
Methods Neonates to whom intravenous CFZ (50 mg/kg) was administered as standard care prior to an invasive procedure were included. Total and unbound CFZ plasma concentrations were determined at ½; 2; 4 and 8 hours after CFZ administration. Linear and multiple regression analyses were used to document covariates of unbound CFZ fraction. For paired analysis of unbound CFZ fractions Wilcoxon signed rank test was used.
Results Forty patients with median weight 2767 (range 830–4200) grams and median postmenstrual age (PMA) 39 (25–45) weeks were included. Median unbound CFZ fraction was 0.39 (0.10–0.73). Linear regression of unbound CFZ fraction versus unbound CFZ plasma concentration (R²=0.39) had a slope significantly different from zero (p<0.001). In a multiple regression analysis, albuminaemia, total CFZ concentration, indirect bilirubinaemia and PMA resulted in an R² value of 0.496. Median unbound CFZ fraction at peak concentration (0.46; range 0.28–0.69) was significantly higher compared to trough level (0.36; range 0.17–0.73) (p<0.001).
Conclusions Between patient and within patient saturability of CFZ protein binding were also documented in neonates. We revealed a median plasma unbound CFZ fraction of 0.39 in neonates, which is higher than reported values in adults. The integration of CFZ protein binding aspects in future pharmacokinetic/pharmacodynamic research is warranted to optimize CFZ dosing, especially in neonates.
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