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

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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; 100mg/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 t1/2β of the two drugs differed significantly, being 29min for ceftriaxone and 17min 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 μg/ml in plasma, whereas saturation for ceftriaxone was seen at lower concentrations.