title: Interindividual changes in volume of distribution of cefazolin in newborn infants and its prediction based on physiological pharmacokinetic concepts.
abstract: 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.
authors.affiliation: Hospital Pharmacy, University of Kanazawa, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Deguchi
authors.forename: R
authors.initials: R
authors.lastname: Koshida
authors.forename: E
authors.initials: E
authors.lastname: Nakashima
authors.forename: R
authors.initials: R
authors.lastname: Watanabe
authors.forename: N
authors.initials: N
authors.lastname: Taniguchi
authors.forename: F
authors.initials: F
authors.lastname: Ichimura
authors.forename: A
authors.initials: A
authors.lastname: Tsuji
mesh_terms: D001798:Blood Proteins / Q000378:metabolism; D002437:Cefazolin / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn / Q000378:metabolism*; D008297:Male; D011485:Protein Binding
chemical_list: D001798:Blood Proteins; D002437:Cefazolin