乳酸环丙沙星在不同程度肾功能受损患者的药动学研究

Pharmacokinetics of ciprofloxacin lactate in patients with impaired renal function

目的 对 2 2例肾功能正常与受损患者单剂量静滴环丙沙星 (ciprofloxacin ,CPFX)的药动学进行研究。方法 按肾功能测定结果将患者分成 4组 :第 1组 (肾功能正常组 ) ,肌酐清除率 (CLCR) >80mL·min-1,n =6 ;第 2组 (肾功能轻度受损组 ) ,CLCR5 1～ 80mL·min-1,n =5 ;第 3组 (肾功能中度受损组 ) ,CLCR2 0～ 5 0mL·min-1,n =6 ;第 4组 (肾功能重度受损组 ) ,CLCR<2 0mL·min-1,n =5。第 1,2 ,3组CPFX的滴注剂量为 40 0mg ,第 4组为 30 0mg ,滴注时间均为 1h。用微生物法测定CPFX的浓度。结果 与肾功能正常组相比 ,其他各组的表观分布容积 (Vc)各组之间均无显著改变 ,第 2组的各药动学参数亦无显著改变 ;但第 3,4组 (肾功能中、重度受损组 )的AUC ,t1/ 2α,t1/ 2 β及CLS 与第 1组相比均显著改变 ,其中AUC分别升高到第 1组的 2 .8和 5 .5倍 ,t1/ 2α分别延长到第 1组的 2 .8和 2 .9倍 ,t1/ 2 β分别延长到第 1组的 1.8和 2 .7倍 ,CLS 分别比第 1组降低了 6 0 %和 81%。结论 当CLCR<5 0mL·min-1时 ,应调整给药方案。对于严重肾衰的患者 (CLCR<2 0mL·min-1)静脉滴注CPFX时 ,建议采用每日一次 ,剂量为 2 0 0mg的给药方案。

OBJECTIVE: The pharmacokinetics of ciprofloxacin (CPFX) was studied in 22 patients with normal and impaired renal function after a single intravenous administration. METHODS: The patients were randomly derived into four groups, basing on their creatinine clearance (CLCR): group 1 (normal renal function), CLCR>80 mL&middotmin-1, n=6; group 2 (mild renal impairment), CLCR51∼80 mL&middotmin-1, n=5; group 3 (moderate renal impairment), CLCR20∼50 mL&middotmin-1, n=6;group 4 (severe renal impairment), CLCR-1n = 5. All patients in group 1, 2 and 3 received a single dose of 400 mg, and group 4 at 300 mg, respectively. CPFX were infused intravenously for 1 h. The serum concentrations of CPFX were determined by bioassay. RESULTS: The apparent volumes of distribution were not significantly different from each other in the four groups (P>0.05). AUC was 2.8 and 5.5 fold, t1/2α was 2.8 and 2.9 fold, and t1/2β was 1.8 and 2.7 fold higher in groups 3 and 4 than those in group 1, significantly and respectively. CLS was 60% and 81% lower in group 3 and 4 than those in group 1. CONCLUSION: A dose of 200 mg CPFX daily was suggested for patients with severely impaired renal function (CLCR-1).