Tigecycline Pharmacokinetics in Subjects With Various Degrees of Renal Function
Tigecycline Pharmacokinetics in Subjects With Various Degrees of Renal Function
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DOI：
10.1177/0091270011416938
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发表时间：
2012-09-01
影响因子：
2.9
通讯作者：
Raible, Donald G.
中科院分区：
文献类型：
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作者：
Korth-Bradley, Joan M.;Troy, Steven M.;Raible, Donald G.
替格环素的药代动力学参数在肾功能严重受损的受试者(肌酐清除量和内生肌酐清除量为30毫升/分钟，n=6)、血液透析受试者(其中4人在血液透析前接受替吉环素治疗，4人在血液透析后接受替吉环素治疗)和年龄调整后肾功能正常的受试者(n=6)在单次服用100 mg剂量后进行评估。连续采集血清和尿样，采用高效液相色谱-串联质谱仪(LC/MS/MS)分析。然后用非隔室药代动力学方法分析血药浓度-时间数据。肾功能正常的受试者替格环素肾清除量约占全身清除量的20%。在有严重肾损害的受试者中，替加环素清除量减少了约20%，替加环素浓度-时间曲线下的面积增加了约30%。替格环素不能通过透析有效地去除；因此，它可以在不考虑血液透析时间的情况下使用。基于这些药代动力学数据，替格环素在肾损害患者中不需要调整剂量。
The pharmacokinetic parameters of tigecycline were assessed in subjects with severe renal impairment (creatinine clearance < 30 mL/min, n = 6), subjects receiving hemodialysis (4 received tigecycline before and 4 received tigecycline after hemodialysis), and subjects with age-adjusted, normal renal function (n = 6) after administration of single 100-mg doses. Serial serum and urine samples were collected and assayed using validated liquid chromatography with tandem mass spectrometer (LC/MS/MS) methods. Concentration-time data were then analyzed using noncompartmental pharmacokinetic methods. Tigecycline renal clearance in subjects with normal renal function represented approximately 20% of total systemic clearance. Tigecycline clearance was reduced by approximately 20%, and area under the tigecycline concentration-time curve increased by approximately 30% in subjects with severe renal impairment. Tigecycline was not efficiently removed by dialysis; thus, it can be administered without regard to timing of hemodialysis. Based on these pharmacokinetic data, tigecycline requires no dosage adjustment in patients with renal impairment.