头孢曲松在大鼠体内的处置：药代动力学-蛋白结合模型的应用及与头孢噻肟的比较。

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

Hakim L, Bourne D W, Triggs E J

Department of Pharmacy, University of Queensland, Australia.

Xenobiotica. 1989 Aug;19(8):815-22. doi: 10.3109/00498258909043142.

Abstract

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.

摘要

在大鼠中测定了头孢曲松的药代动力学特征和蛋白结合参数，并与头孢噻肟的进行了比较。2. 头孢曲松和头孢噻肟（单次静脉推注；各100mg/kg）的血药浓度-时间曲线用二室蛋白结合模型进行描述。3. 头孢曲松的校正稳态分布容积（ml/kg）低于头孢噻肟。两种药物的AUC相似。两种药物的t1/2β有显著差异，头孢曲松为29分钟，头孢噻肟为17分钟。4. 两种药物的体内蛋白结合常数相似，但蛋白结合位点的浓度有显著差异。头孢曲松和头孢噻肟在血浆中的平均游离分数（Fp）分别为0.22和0.48。5. 据估计，头孢噻肟在血浆中的结合位点饱和度约在30μg/ml时出现，而头孢曲松在较低浓度时就出现饱和度。