Goonetilleke A K, Dev D, Aziz I, Hughes C, Smith M J, Basran G S
Respiratory Unit, Rotherham General Hospitals (NHS) Trust, South Yorkshire, UK.
J Antimicrob Chemother. 1996 Dec;38(6):969-76. doi: 10.1093/jac/38.6.969.
Pleural fluid and serum pharmacokinetics of ceftriaxone were performed in thirteen patients with pleural effusion. One gram of ceftriaxone was administered once daily intravenously in six patients and intramuscularly in seven patients. Ceftriaxone concentrations were measured in serum and pleural fluids in both groups on the first day of administration and in four patients of the intramuscular group on the fourth day of administration. The mean serum peak concentration at 1 h was 199 mg/L (S.E.M. 63.2) in the iv group and 80.5 mg/L (S.E.M. 12.0) in the im group. The mean serum trough concentrations in the two groups at 24 h were 27.5 mg/L (S.E.M. 12.6) and 29.7 mg/L (S.E.M. 5.2) respectively. In the pleural fluid, mean peak concentration was 20.1 mg/L (S.E.M. 4.7) at 6 h in the iv group and 15.3 mg/L (S.E.M. 5.1) at 12 h in the im group. The mean trough concentration was 9.6 mg/L (S.E.M. 1.9) and 13.3 mg/L (S.E.M. 3.1) at 24 h in the two groups respectively. On the fourth day of intramuscular administration the serum and pleural fluid peak and trough concentrations were higher when compared with the first day, consistent with a cumulative effect. The serum and pleural fluid concentrations of ceftriaxone following intravenous and intramuscular administration were well above the MIC90 of most common respiratory pathogens indicating good penetration into extracellular spaces. Further, these serum and pleural fluid antibiotic concentrations could be maintained even after a single intramuscular injection of the drug, thus indicating its usefulness as a parenteral mode of therapy on a domicilliary basis with a significant cost-saving potential. In conclusion, intramuscular administration of ceftriaxone would appear to be a convenient method of administering parenteral therapy in lower respiratory tract infections in the hospital and community, with pharmacokinetics very similar to those exhibited by the intravenous route.
对13例胸腔积液患者进行了头孢曲松的胸腔积液和血清药代动力学研究。6例患者每日静脉注射1克头孢曲松，7例患者每日肌肉注射1克头孢曲松。在给药第一天，对两组患者的血清和胸腔积液中的头孢曲松浓度进行了测量，并在肌肉注射组的4例患者给药第四天进行了测量。静脉注射组1小时时的平均血清峰浓度为199毫克/升（标准误63.2），肌肉注射组为80.5毫克/升（标准误12.0）。两组24小时时的平均血清谷浓度分别为27.5毫克/升（标准误12.6）和29.7毫克/升（标准误5.2）。在胸腔积液中，静脉注射组6小时时的平均峰浓度为20.1毫克/升（标准误4.7），肌肉注射组12小时时为15.3毫克/升（标准误5.1）。两组24小时时的平均谷浓度分别为9.6毫克/升（标准误1.9）和13.3毫克/升（标准误3.1）。在肌肉注射给药第四天，血清和胸腔积液的峰浓度和谷浓度与第一天相比更高，这与累积效应一致。静脉注射和肌肉注射后头孢曲松的血清和胸腔积液浓度远高于大多数常见呼吸道病原体的MIC90，表明其对细胞外间隙有良好的穿透性。此外，即使单次肌肉注射该药物后，这些血清和胸腔积液中的抗生素浓度也能维持，因此表明其作为一种非住院治疗的胃肠外给药方式具有显著的成本节约潜力。总之，肌肉注射头孢曲松似乎是在医院和社区中对下呼吸道感染进行胃肠外治疗的一种方便方法，其药代动力学与静脉注射途径非常相似。
