Disposition of ceftriaxone in rat: Application of a pharmacokinetic-protein binding model and comparison with cefotaxime

Abstract

1. The pharmacokinetic profile and protein binding parameters of ceftriaxone were determined in rat, and compared with those of cefotaxime. 2. Plasma concentration-time curves of ceftriaxone and cefotaxime (single i.v. bolus; 100 mg/kg each) were described by a two-compartment, protein-binding model. 3. The corrected VTss (ml/kg) of ceftriaxone was lower than that of cefotaxime. The AUCs of both drugs were similar. The t1/2 beta of the two drugs differed significantly, being 29 min for ceftriaxone and 17 min for cefotaxime. 4. In vivo protein binding constants of both drugs were similar, but the concentrations of protein binding sites differed significantly. The average free fractions in plasma (Fp) of ceftriaxone and cefotaxime were 0.22 and 0.48 respectively. 5. Saturation of the binding site for cefotaxime was estimated to occur at about 30 micrograms/ml in plasma, whereas saturation for ceftriaxone was seen at lower concentrations.

Comparison of Plasma and Free Tissue Levels of Ceftriaxone in Rats by Microdialysis

“…This result differs from other investigators who use a single-site binding model and report different values for both protein binding constants k and p, depending on high or low concentrations. 26 The in vivo recovery of ceftriaxone was up to three times lower (7.1-10.6%) than in vitro (21.0%) at a flow rate of 1.5 µL/min, and the higher flow rate showed similar results. This result differs from our findings with piperacillin, a -lactam antibiotic with a penam backbone, which showed similar results for in vivo and in vitro recovery.…”

LB11058, a New Cephalosporin with High Penicillin-Binding Protein 2a Affinity and Activity in Experimental Endocarditis Due to Homogeneously Methicillin-Resistant Staphylococcus aureus

“…However, binding became saturable and free drug substantially increased above these cutoff concentrations. By comparison, vancomycin was bound in rat serum at 40% (21), and ceftriaxone was bound in rat serum at 80% (18). Thus, we inferred that, based on an MIC of 1 mg of LB11058/liter for MRSA, the concentrations of LB11058 in the serum of rats should be close to 250 mg/liter or more in order to be effective.…”

“…We conclude that PBP2a-blocking beta-lactams are likely to become very promising new compounds against multiresistant staphylococci, including S. aureus and all coagulase-negative species (9,10,15,22,31,33). (18,21). c ‫,ء‬ P Ͻ 0.05 compared to either controls or low-dose LB11058.…”

“…These values were subtracted to total drug concentrations for the calculation of protein binding. Serum binding of vancomycin (40%) and ceftriaxone (80%) were extrapolated from previous literature (18,21).…”

Enhanced Oral Bioavailability of Poorly Absorbed Drugs. I. Screening of Absorption Carrier for the Ceftriaxone Complex

“…or intramuscular injections. Ceftriaxone (CTX) is a broad‐spectrum third‐generation cephalosporin antibiotic and is only available for parenteral administration because of its sensitivity to degradation in gastric fluid and poor absorption from the intestinal tract 6–10. Many β‐lactam antibiotics which possess peptide‐like chemical structures are transported by peptide transporter PEPT1 expressed in the luminal membrane of enterocytes.…”