Protein binding of cefazolin is saturable in vivo both between and within patients

• Published in: British journal of clinical pharmacology Vol. 63; no. 6; pp. 753 - 757
• Main Authors: Vella‐Brincat, Jane W. A., Begg, Evan J., Kirkpatrick, Carl M. J., Zhang, Mei, Chambers, Stephen T., Gallagher, Kate
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2007; Blackwell Science; Blackwell Science Inc
• Subjects: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents - blood; Anti-Bacterial Agents - therapeutic use; antibiotics; Biological and medical sciences; Blood Proteins - drug effects; Blood Proteins - metabolism; cefazolin; Cefazolin - blood; Cefazolin - therapeutic use; cephalosporins; Female; Humans; Male; Medical sciences; Middle Aged; New Zealand; Pharmacokinetics; Pharmacology. Drug treatments; protein binding; Protein Binding - drug effects; New Zealand; Human; In vivo; Binding protein; Antibiotic; Cephalosporin derivatives; Cefazolin; β-Lactams; Antibacterial agent; protein binding; antibiotics; cephalosporins
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/j.1365-2125.2006.02827.x

Aims The aims of the study were a) to determine if there is evidence of saturable protein binding of cefazolin in plasma across the range of concentrations achieved clinically (between patient variability) and b) to investigate whether saturable protein binding is also evident from trough and peak concentrations in the same patient (within patient variability). Methods Unbound and total plasma concentrations were measured in patients who were treated with cefazolin intravenously by continuous infusion or intermittent injection. In study (i) single random samples were taken from one series of patients. In study (ii) paired samples (troughs and peaks) were taken from a second series of patients. Results Thirty‐one patients were included in study (i). Linear regression analysis of the percentage unbound vs. unbound plasma concentrations revealed a slope significantly different from zero, suggesting saturable protein binding. Mean values for percentage unbound ranged from 9% at low concentrations (8.5 mg l−1) to 51% at high concentrations (140 mg l−1). Twelve patients were investigated in study (ii). Values for protein binding ranged from 85% at low concentrations (2.7 mg l−1) to 52% at high concentrations (200.3 mg l−1). The percentage unbound was significantly higher (P < 0.0001) at high (peak) concentrations than at lower (trough) concentrations, confirming saturable protein binding. Conclusions The protein binding of cefazolin is saturable in vivo in humans, both between and within patients.