LeBel M, Grégoire S, Caron M, Bergeron M G
Antimicrob Agents Chemother. 1985 Jul;28(1):123-7. doi: 10.1128/AAC.28.1.123.
Plasma and suction skin blister fluid concentrations of ceftriaxone were studied in 12 subjects after intravenous administration of 1 g of ceftriaxone every 12 h (q12h) and 2 g every 24 h (q24h) after single and multiple doses. Ceftriaxone concentrations were determined by high-pressure liquid chromatography. Mean peak plasma concentrations (at the end of the 5-min infusion) were 254.0 and 374.8 micrograms/ml after administration of 1 g q12h after single and multiple doses, respectively. Similarly, with 2 g q24h, maximum levels were 409.6 and 443.5 micrograms/ml. Forty-eight hours after the last dose of ceftriaxone, plasma concentrations were still detectable: 1.2 micrograms/ml after 1 g q12h and 3.0 micrograms/ml after 2 g q24h. Higher ceftriaxone concentrations were observed in blister fluid after multiple doses than after a single dose. Peak concentrations almost doubled in the blister fluid after multiple doses: 36.0 versus 67.0 micrograms/ml and 38.6 versus 68.9 micrograms/ml for 1 g q12h and 2 g q24h, respectively. Elimination half-life of ceftriaxone in the blister (8.3 and 11.5 h) was longer than plasma half-life (6.3 h). With the area under the concentration-time curve ratio, a 113% increase in tissue penetration was observed after multiple doses for the 1 g q12h regimen. The free plasma and blister fluid ceftriaxone concentrations observed at the end of the dosing interval of the 2 g q24h regimen were higher than the MIC for 90% of the susceptible microorganisms and justified the once-a-day use of ceftriaxone.
在12名受试者中，研究了单次和多次静脉注射头孢曲松后的血浆及皮肤水疱抽吸液中的头孢曲松浓度。单次和多次给药后，每12小时（q12h）静脉注射1g头孢曲松以及每24小时（q24h）静脉注射2g头孢曲松。采用高压液相色谱法测定头孢曲松浓度。单次和多次给药后，q12h给药1g时，平均血浆峰浓度（在5分钟输注结束时）分别为254.0和374.8μg/ml。同样，q24h给药2g时。最高血药浓度分别为409.6和443.5μg/ml。在最后一剂头孢曲松给药48小时后，血浆浓度仍可检测到：q12h给药1g后为1.2μg/ml，q24h给药2g后为3.0μg/ml。多次给药后水疱液中的头孢曲松浓度高于单次给药后。多次给药后水疱液中的峰浓度几乎翻倍：q12h给药1g时分别为36.0和67.0μg/ml，q24h给药2g时分别为38.6和68.9μg/ml。头孢曲松在水疱中的消除半衰期（8.3和11.5小时）长于血浆半衰期（6.3小时）。根据浓度 - 时间曲线下面积比，q12h给药1g方案多次给药后组织穿透率增加了113%。q24h给药2g方案给药间隔结束时观察到的游离血浆和水疱液头孢曲松浓度高于90%敏感微生物的最低抑菌浓度，这证明了头孢曲松每日一次使用的合理性。
