Frimodt-Møller N, Bentzon M W, Thomsen V F
Department of Antibiotics, Statens Seruminstitut, Copenhagen, Denmark.
Acta Pathol Microbiol Immunol Scand B. 1987 Oct;95(5):261-7. doi: 10.1111/j.1699-0463.1987.tb03123.x.
In a mouse model using intraperitoneal inoculation of Streptococcus pneumoniae type 3, the 50% effective dose, ED50, after single doses one hour post-inoculation was considerably lower for ceftriaxone (CRO) than for cefuroxime (CXM) and cefotaxime (CTX), in spite of the same minimal inhibitory concentration, MIC, of 0.02 mcg/ml against the pneumococcus for all 3 drugs. The bactericidal activity as measured by time-kill curves was similar for the 3 drugs, as was the post-antibiotic effect in vitro. Protein binding in mouse serum was considerably higher for CRO (87%) than for both CTX (35%) and CXM (15%), respectively. Of pharmacokinetic parameters investigated on doses equal to the ED50s, the time the serum antibiotic concentration remained above the MIC (delta T(MIC)) was the factor that varied the least among 3 drugs. Therefore, the superior in vivo effect for CRO is not due to higher intrinsic activity against the pathogen but to the long serum-elimination half-life resulting in an extended delta T(MIC), probably related to the high serum protein binding.
在一个通过腹腔接种3型肺炎链球菌建立的小鼠模型中，接种后1小时单次给药时，头孢曲松（CRO）的50%有效剂量（ED50）显著低于头孢呋辛（CXM）和头孢噻肟（CTX），尽管这三种药物对肺炎球菌的最低抑菌浓度（MIC）均为0.02 mcg/ml。通过时间杀菌曲线测定的杀菌活性，这三种药物相似，体外抗生素后效应也相似。在小鼠血清中，CRO的蛋白结合率（87%）分别显著高于CTX（35%）和CXM（15%）。在等于ED50的剂量下研究的药代动力学参数中，血清抗生素浓度保持高于MIC的时间（ΔT(MIC)）是三种药物中变化最小的因素。因此，CRO体内效果优越并非由于对病原体的内在活性更高，而是由于血清消除半衰期长导致ΔT(MIC)延长，这可能与高血清蛋白结合率有关。
