Montay G
Drug Metabolism and Pharmacokinetic Department, Rhône-Poulenc Rorer, Antony, France.
J Antimicrob Chemother. 1996 May;37 Suppl A:27-39. doi: 10.1093/jac/37.suppl_a.27.
In Caucasian volunteers and patients plasma sparfloxacin concentrations reached a peak of 1.2-1.5 mg/L between 3 and 6 h after a single 400 mg dose; T1/2 ranged from 16 to 22 h. The peak plasma concentration and the area under the plasma concentration-time curve exhibited dose-related increases but a slight decrease in the extent of absorption was observed following administration of doses above those recommended for clinical use. Renal clearance did not exceed 10% of the apparent plasma clearance. The urinary excretion of unchanged drug accounted for 9-10% of the dose administered and that of its glucuronide for 27-38% of the dose. The biliary excretion of the drug and its glucuronide accounted for about 1.5 and 11% of the dose administered, respectively. Following multiple-dose administration (200 mg daily after a loading dose of 400 mg on day 1), steady-state concentrations were achieved following the second dose. The peak plasma concentration was 1.4 mg/L and the through concentration was 0.5 mg/L. The T1/2 was approximately 20 h. Studies in patients show that the pharmacokinetics of sparfloxacin were not influenced by age but severe renal failure markedly impaired elimination of the parent drug (the T1/2 was approximately doubled in patients with renal failure), and glucuronide, requiring adjustment of the dosage regimen. In patients with liver cirrhosis but no cholestasis, the pharmacokinetics of sparfloxacin were not markedly altered, although the urinary excretion of the glucuronide was about twice that observed in healthy volunteers. No modification of the usual dosage is recommended for these patients.
在白种人志愿者和患者中，单次服用400mg剂量后，血浆司帕沙星浓度在3至6小时内达到峰值1.2 - 1.5mg/L；半衰期为16至22小时。血浆峰浓度和血浆浓度-时间曲线下面积呈现剂量相关增加，但在给予高于临床推荐剂量后，吸收程度略有下降。肾清除率不超过表观血浆清除率的10%。原形药物的尿排泄量占给药剂量的9 - 10%，其葡萄糖醛酸结合物的尿排泄量占给药剂量的27 - 38%。药物及其葡萄糖醛酸结合物的胆汁排泄量分别约占给药剂量的1.5%和11%。多次给药（第1天给予400mg负荷剂量后，每日200mg）后，第二次给药后达到稳态浓度。血浆峰浓度为1.4mg/L，谷浓度为0.5mg/L。半衰期约为20小时。患者研究表明，司帕沙星的药代动力学不受年龄影响，但严重肾衰竭显著损害原形药物的消除（肾衰竭患者的半衰期约增加一倍），以及葡萄糖醛酸结合物的消除，需要调整给药方案。在无胆汁淤积的肝硬化患者中，司帕沙星的药代动力学没有明显改变，尽管葡萄糖醛酸结合物的尿排泄量约为健康志愿者的两倍。不建议对这些患者调整常规剂量。
