Jacolot A, Incagnoli P, Edouard A R, Tod M, Petitjean O, Samii K, Mimoz O
Service d'Anesthésie-Réanimation, Hôpital Bicêtre, Le Kremlin Bicêtre, France.
Intensive Care Med. 1999 May;25(5):486-91. doi: 10.1007/s001340050885.
To determine the pharmacokinetic parameters of cefpirome, a new so-called fourth-generation cephalosporin, in previously healthy trauma patients with posttraumatic systemic inflammatory response syndrome (SIRS) and to compare them to parameters obtained in matched, healthy volunteers.
A prospective study.
12-bed surgical intensive care unit in a university hospital.
9 severe [Injury Severity Score, median (range) 29 (16-50)] trauma patients on mechanical ventilation with proven or suspected cefpirome-susceptible nosocomial infection, with no renal or hepatic failure, and healthy volunteers matched for age (+/- 5 years), sex, and body surface area (+/- 10%) were enrolled. All were men.
Cefpirome (2 g twice daily) was continuously infused over a 0.5 h period alone or concomitantly with ciprofloxacin (400 mg over 1 h, twice daily).
Antibiotic concentrations in plasma were measured by high-performance liquid chromatography; their pharmacokinetic parameters were evaluated at 12 time points after the first drug administration using a noncompartmental model. Cefpirome pharmacokinetic parameters for the two groups were similar despite a wider variation for trauma patients. Specifically, the median (range) time during which the cefpirome concentration in plasma remained over 4 mg/l (corresponding to the French lower cutoff determining cefpirome susceptibility) was 9.5 (7- > 12) and 9 (8-12) h for trauma patients and healthy volunteers, respectively. In the group of five patients receiving combined antibiotic therapy, the interindividual variability of pharmacokinetics was wider for ciprofloxacin than for cefpirome.
No major pharmacokinetic modification was noted when cefpirome was given to trauma patients with posttraumatic SIRS without significant organ failure, indicating that no dosage adjustment seems required in this population. However, larger studies including determination of antibiotic levels in tissues are warranted to confirm these results.
测定新型所谓第四代头孢菌素头孢匹罗在既往健康的创伤后全身炎症反应综合征（SIRS）创伤患者中的药代动力学参数，并将其与在匹配的健康志愿者中获得的参数进行比较。
一项前瞻性研究。
大学医院的12张床位的外科重症监护病房。
9例严重[损伤严重度评分，中位数（范围）29（16 - 50）]创伤患者，接受机械通气，有已证实或疑似对头孢匹罗敏感的医院感染，无肾衰竭或肝功能衰竭，以及年龄（±5岁）、性别和体表面积（±10%）匹配的健康志愿者入组。均为男性。
头孢匹罗（每日2次，每次2 g）单独在0.5小时内持续输注，或与环丙沙星（1小时内400 mg，每日2次）同时输注。
采用高效液相色谱法测定血浆中的抗生素浓度；使用非房室模型在首次给药后的12个时间点评估其药代动力学参数。尽管创伤患者的变异性更大，但两组的头孢匹罗药代动力学参数相似。具体而言，血浆中头孢匹罗浓度保持在4 mg/l以上（对应法国确定头孢匹罗敏感性的下限）的中位数（范围）时间，创伤患者为9.5（7 - >12）小时，健康志愿者为9（8 - 12）小时。在接受联合抗生素治疗的5例患者组中，环丙沙星的药代动力学个体间变异性比头孢匹罗更大。
在无明显器官衰竭的创伤后SIRS创伤患者中给予头孢匹罗时，未观察到主要的药代动力学改变，表明该人群似乎无需调整剂量。然而，需要开展包括测定组织中抗生素水平的更大规模研究来证实这些结果。
