Goldfarb J, Stern R C, Reed M D, Yamashita T S, Myers C M, Blumer J L
Am J Med. 1987 Apr 27;82(4A):174-9.
Ciprofloxacin has potent in vitro activity against Pseudomonas aeruginosa and Pseudomonas cepacia strains isolated from cystic fibrosis patients. Our previous single-dose pharmacokinetic and pharmacodynamic studies identified important differences between cystic fibrosis patients and age- and sex-matched controls. Based on these data, 30 acutely ill cystic fibrosis patients (aged 18 to 44 years) received 750 mg of ciprofloxacin orally every eight hours for 21 days. Multiple timed serum, urine, and sputum samples for pharmacokinetic analysis were obtained on Days 3, 12, 14, and 21 of the study. Estimates of steady-state pharmacokinetic parameters averaged (+/- SD): t1/2 beta, 3.8 (1) hours; Vd/F, 4.4 (2) liters/kg; Cl/F, 772.9 (301) ml/minute/1.73 m2; Fe, 46 percent; peak, 5.4 (2) mg/liter; and trough, 1.8 (0.8) mg/liter. Serum ciprofloxacin concentrations and pharmacokinetic estimates remained unchanged throughout the study. Sputum ciprofloxacin concentrations exceeded those observed in serum. Sputum cultures revealed 43 P. aeruginosa (MIC90 = 2 micrograms/ml) and 15 P. cepacia (MIC90 = 16 micrograms/ml) strains. Sputum ciprofloxacin concentrations exceeded the MIC90 for P. aeruginosa approximately fivefold, yet only eight isolates were fully suppressed. Posttreatment sputum cultures revealed 35 P. aeruginosa (MIC90 = 16 micrograms/ml) and 15 P. cepacia (MIC90 = 16 micrograms/ml). All patients showed clinical improvement based upon the results of pulmonary function tests and an acute clinical efficacy score (median pre 49/post 60). No patients experienced drug-related toxicity. Ciprofloxacin monotherapy is effective for the acute treatment of cystic fibrosis patients. The development of pathogen resistance during oral therapy may limit its utility in ambulatory patients.
环丙沙星对从囊性纤维化患者中分离出的铜绿假单胞菌和洋葱伯克霍尔德菌菌株具有强大的体外活性。我们之前的单剂量药代动力学和药效学研究确定了囊性纤维化患者与年龄和性别匹配的对照组之间的重要差异。基于这些数据，30名急性病囊性纤维化患者（年龄18至44岁）每8小时口服750毫克环丙沙星，共21天。在研究的第3、12、14和21天获取多个定时血清、尿液和痰液样本进行药代动力学分析。稳态药代动力学参数估计平均值（±标准差）为：t1/2β，3.8（1）小时；Vd/F，4.4（2）升/千克；Cl/F，772.9（301）毫升/分钟/1.73平方米；Fe，46%；峰值，5.4（2）毫克/升；谷值，1.8（0.8）毫克/升。在整个研究过程中，血清环丙沙星浓度和药代动力学估计值保持不变。痰液中环丙沙星浓度超过血清中观察到的浓度。痰液培养显示43株铜绿假单胞菌（MIC90 = 2微克/毫升）和15株洋葱伯克霍尔德菌（MIC90 = 16微克/毫升）菌株。痰液中环丙沙星浓度超过铜绿假单胞菌的MIC90约五倍，但仅8株分离株被完全抑制。治疗后痰液培养显示35株铜绿假单胞菌（MIC90 = 16微克/毫升）和15株洋葱伯克霍尔德菌（MIC90 = 16微克/毫升）。根据肺功能测试结果和急性临床疗效评分（治疗前中位数49/治疗后中位数60），所有患者均显示临床改善。无患者出现药物相关毒性。环丙沙星单药治疗对囊性纤维化患者的急性治疗有效。口服治疗期间病原体耐药性的出现可能会限制其在门诊患者中的应用。
