Reed M D, Stern R C, Myers C M, Yamashita T S, Blumer J L
Division of Pediatric Pharmacology and Critical Care, Rainbow Babies and Childrens Hospital, Cleveland, OH 44106.
J Clin Pharmacol. 1988 Aug;28(8):691-9. doi: 10.1002/j.1552-4604.1988.tb03202.x.
The single-dose pharmacokinetics of oral ciprofloxacin 750 mg were evaluated in six subjects with cystic fibrosis (CF subjects) and six age, sex and approximate weight-matched control subjects (controls). In addition, the effect of concurrently administered oral pancreatic enzyme replacement on the pharmacokinetics of ciprofloxacin was studied in 12 CF subjects. Ciprofloxacin t1/2, VSSF, CLF, and CLR in the matched CF subjects averaged 4.5 hours, 2.8 L/kg, 2.73 mL/min/kg and 5.7 mL/min/kg, respectively. Forty-two percent of the ciprofloxacin dose was excreted in the urine (0-48 hours) as the parent compound. No statistically significant differences in these ciprofloxacin pharmacokinetic parameter estimates were observed between CF and control subjects. In three CF subjects and two controls, the urinary excretion of ciprofloxacin and four of its metabolities were similar. In contrast, CF subjects demonstrated a prolonged tmax (2.3 versus 1.3 hours P less than .05) though ciprofloxacin Cmax was similar (4.7 versus 3.8 mg/L, NS). The concurrent administration of oral pancreatic enzyme replacement had no effect on the pharmacokinetics of ciprofloxacin. Apparent ciprofloxacin pharmacokinetic parameters in sputum were similar to those observed in serum. Sputum ciprofloxacin concentrations lagged behind serum concentrations but, on average, exceeded serum concentrations for 20 hours of the 24-hour sampling period. These sputum ciprofloxacin concentrations exceeded the reported MIC90 for Pseudomonas aeruginosa for approximately 15 hours. These data suggest an oral ciprofloxacin dose of 750 mg administered q8h to promote accumulation and maintenance of sputum drug concentrations well above pathogen MICs for the majority of a dosing interval in patients with CF.
在6名囊性纤维化患者（CF患者）和6名年龄、性别及体重相近的对照受试者（对照组）中评估了口服750mg环丙沙星的单剂量药代动力学。此外，还在12名CF患者中研究了同时服用口服胰酶替代剂对环丙沙星药代动力学的影响。配对的CF患者中环丙沙星的半衰期、稳态分布容积、肺清除率和肾清除率平均分别为4.5小时、2.8L/kg、2.73mL/（min·kg）和5.7mL/（min·kg）。42%的环丙沙星剂量在尿液中（0 - 48小时）以母体化合物形式排泄。CF患者和对照受试者之间在这些环丙沙星药代动力学参数估计值上未观察到统计学上的显著差异。在3名CF患者和2名对照中，环丙沙星及其4种代谢物的尿排泄情况相似。相比之下，CF患者的达峰时间延长（2.3小时对1.3小时，P<0.05），尽管环丙沙星的峰浓度相似（4.7mg/L对3.8mg/L，无统计学意义）。同时服用口服胰酶替代剂对环丙沙星的药代动力学无影响。痰液中环丙沙星的表观药代动力学参数与血清中观察到的相似。痰液中环丙沙星浓度滞后于血清浓度，但在24小时采样期内平均有20小时超过血清浓度。这些痰液中环丙沙星浓度超过了报道的铜绿假单胞菌的MIC90约15小时。这些数据表明，对于CF患者，每8小时口服750mg环丙沙星可促进痰液药物浓度的积累和维持，使其在大多数给药间隔内远高于病原体的MIC。
