Cefazolin plasma protein binding and its covariates in neonates

A. Smits*, A. Kulo, R. Verbesselt, G. Naulaers, J. De Hoon, P. Vermeersch, K. Allegaert

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

28 Citations (Scopus)

Abstract

Cefazolin (CFZ) is highly and saturably bound to human serum albumin (HSA) in adults. We aim to describe CFZ protein binding and its covariates in neonates. In neonates to whom intravenous CFZ (50 mg/kg) was administered prior to a surgical procedure, total and unbound CFZ plasma concentrations (mg/l)were determined at0.5, 2, 4 and 8 h after CFZ administration. Linear and multiple regression analyses were used to document covariates of unbound CFZ fraction. The Wilcoxon signed-rank test was used for the paired analysis of unbound CFZ fractions. In 40 patients with a median weight of 2,767 (range 830-4,200) g and a postmenstrual age (PMA) of 39 (25-45) weeks, 131 samples were collected. The median unbound CFZ fraction was 0.39 (0.10-0.73). Linear regression of unbound CFZ fraction versus unbound CFZ plasma concentration (R200.39) 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. The median unbound CFZ fraction at the peak concentration (0.46, range 0.28-0.69) was significantly higher compared to the trough level (0.36, range 0.17-0.73) (p<0.001). The between- and within-patient saturability of CFZ plasma protein binding were documented in neonates. The median unbound CFZ fraction in neonates is higher than in adults and depends partly on albuminaemia, total CFZ concentration, indirect bilirubinaemia and PMA. Integration of CFZ protein binding in future pharmacokinetic/pharmacodynamic research is warranted in order to optimise neonatal CFZ dosing. We recommend protein binding assessment in the neonatal pharmacokinetic evaluation of highly protein-bound or clinically relevant drugs.

Original languageEnglish
Pages (from-to)3359-3365
Number of pages7
JournalEuropean Journal of Clinical Microbiology and Infectious Diseases
Volume31
Issue number12
DOIs
Publication statusPublished - Dec 2012
Externally publishedYes

Bibliographical note

Funding Information:
Karel Allegaert was supported by the Fund for Scientific Research, Flanders (Belgium) (FWO Vlaanderen), by a Fundamental Clinical Investigatorship (1800209N) and a research grant (1506409N). Aida Kulo was supported by a JoinEU-SEE scholarship. None of the authors have any other conflict of interest related to this paper.

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