Interindividual changes in volume of distribution of cefazolin in newborn infants and its prediction based on physiological pharmacokinetic concepts

✍ Scribed by Yoshiharu Deguchi; Rie Koshida; Emi Nakashima; Reiji Watanabe; Noboru Taniguchi; Fujio Ichimura; Akira Tsuji

• Publisher: John Wiley and Sons
• Year: 1988
• Tongue: English
• Weight: 521 KB
• Volume: 77
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600770807

✦ Synopsis

The purpose of this study was to investigate factors affecting the volume of distribution of cefazolin (a beta-lactam antibiotic) in newborn infants with bacterial infections, and to propose a method for predicting the volume of distribution at steady state per body weight (Vdss/BW). Cefazolin and tobramycin (an aminoglycoside) were simultaneously given to newborn infants (aged 2 to 28 d), and plasma concentration-time data were analyzed on the basis of model-independent moment analysis. The Vdss/BW values ranged from 0.212 to 0.373 L/kg for cefazolin and from 0.384 to 0.541 L/kg for tobramycin. The unbound fraction of cefazolin in plasma (fp) fluctuated widely, from 0.22 to 0.83, among patients. The Vdss/BW value for cefazolin was characterized by both large extracellular water volume and a remarkable change in fp, and could be predicted as a function of fp using physiological pharmacokinetic concepts. Moreover, interindividual changes in the unconjugated bilirubin:albumin molar ratio were predominantly responsible for the individual variation in the fp values of cefazolin in newborn infants.