The Influence of Dirithromycin on the Pharmacokinetics of Cyclosporine in Healthy Subjects and in Renal Transplant Patients.
The Influence of Dirithromycin on the Pharmacokinetics of Cyclosporine in Healthy Subjects and in Renal Transplant Patients.
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地红霉素对健康受试者和肾移植患者中环孢素药代动力学的影响。
DOI：
10.1097/00045391-199506000-00009
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发表时间：
1995
影响因子：
4.2
通讯作者：
R. Shapiro
中科院分区：
文献类型：
--
作者：
K. Bachmann;T. Sullivan;J. Reese;L. Jauregui;K. Miller;M. Scott;G. Sides;R. Shapiro
在健康年轻男性中研究了研究中的大环内酯类抗生素地红霉素的标准治疗方案对口服环孢素 (CSA) 单剂量动力学的影响，以及对一组肾移植患者中环孢素稳态处置动力学的影响。八名男性志愿者在知情同意后参与。 CSA 在三个阶段中的每个阶段中以三个单剂量（每次 15 mg kg（负号 1）口服）施用：（1）在 14 天的地红霉素治疗之前； (2) 地红霉素 14 天疗程结束时（500 mg p.o. qAM）； (3) 地红霉素 14 天疗程最后一次给药后 2 周。估计 CSA 的药代动力学参数，并通过变异分析评估治疗之间的差异。治疗（阶段）平均值之间没有检测到显着差异（p < 0.05）。我们得出的结论是，当健康的年轻成年男性口服地红霉素时，典型的 14 天地红霉素治疗方案未能改变 CSA 的处置动力学。在 15 名稳定的肾移植患者中研究了地红霉素标准方案对口服 CSA 稳态处置动力学的影响。在停止 14 天（500 mg 天（减号 1））地红霉素口服方案之前、期间和之后 2 周评估 CSA 的药代动力学参数。地红霉素引起以下参数的微小但显着的变化：地红霉素治疗期间 C(av) 增加了 16%，并且标准化 C(av) 的变化具有可比性。同样，地红霉素治疗期间 C(SS,min) 和标准化 C(SS,min) 分别增加 19% 和 20%。地红霉素治疗期间 CSA 口腔清除率 CL/F(SS) 下降 17%。地红霉素治疗期间 C(SS,max) 和标准化 C(SS,max) 分别增加 13% 和 17%，但与地红霉素治疗前后没有显着差异。在环孢素浓度的治疗范围内考虑时，地红霉素治疗期间 CSA 的药代动力学变化幅度（正常受试者<15%，肾移植患者 15--20%）相对较小，除了常规全血 CSA 和血清肌酐监测外，不太可能需要特别注意此类患者的 CSA 剂量。
The effect of a standard regimen of the investigational macrolide antibiotic, dirithromycin, on the single-dose kinetics of orally administered cyclosporine (CSA) was investigated in healthy young males and on the steady-state disposition kinetics of cyclosporine in a panel of renal transplant patients. Eight male volunteers participated after giving informed consent. CSA was administered in three single doses (15 mg kg(minus sign1) p.o. each) in each of three phases: (1) prior to a 14-day regimen of dirithromycin; (2) at the end of a 14-day regimen of dirithromycin (500 mg p.o. qAM); and (3) 2 weeks after the last dose of a 14-day regimen of dirithromycin. Pharmacokinetic parameters of CSA were estimated, and the differences among treatments were assessed by analysis of variation. No significant differences among treatment (phase) means were detected (p < 0.05). We conclude that a typical 14-day regimen of dirithromycin failed to alter the disposition kinetics of CSA when taken orally healthy young adult males. The effect of a standard regimen of dirithromycin on the steady-state disposition kinetics of orally administered CSA was investigated in a panel of 15 stable renal transplant patients. Pharmacokinetic parameters for CSA were evaluated prior to, during, and 2 weeks after discontinuing a 14-day (500 mg day(minus sign1)) oral regimen of dirithromycin. Dirithromycin elicited small but significant changes in the following parameters: C(av) was increased by 16% during dirithromycin treatment, and the changes in normalized C(av) were comparable. Likewise, C(SS,min) and normalized C(SS,min) were increased by 19% and 20%, respectively, during dirithromycin treatment. CSA oral clearance, CL/F(SS), decreased by 17% during dirithromycin treatment. C(SS,max) and normalized C(SS,max) were increased by 13% and 17%, respectively, during dirithromycin treatment but were not significantly different from those either before or after dirithromycin. The magnitude of the pharmacokinetic changes for CSA during dirithromycin treatment (<15% in normal subjects and 15--20% in renal transplant patients) when considered in the context of the therapeutic range of cyclosporine concentrations was relatively small, and not likely to warrant special attention to the dosing of CSA in such patients beyond routine whole-blood CSA and serum creatinine monitoring.