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罗红霉素与环孢素在心脏移植患者中的相互作用。

Interaction between roxithromycin and cyclosporin in heart transplant patients.

作者信息

Billaud E M, Guillemain R, Fortineau N, Kitzis M D, Dreyfus G, Amrein C, Kreft-Jaïs C, Husson J M, Chrétien P

机构信息

Department of Clinical Pharmacology, Broussais Hospital, Paris, France.

出版信息

Clin Pharmacokinet. 1990 Dec;19(6):499-502. doi: 10.2165/00003088-199019060-00006.

Abstract

Cyclosporin is an immunosuppressive agent commonly used in transplant patients. It is actively metabolised by the cytochrome P450 system and interactions with drugs metabolised by the same system are predictable. This is particularly relevant since cyclosporin has a low therapeutic index and its renal toxicity is concentration-related. Roxithromycin, a new, well-tolerated macrolide with a weak interactive profile, uses the same isoenzyme of the P450 system as cyclosporin. To evaluate its interaction potential in clinical practice, 8 heart transplant recipients treated with cyclosporin for at least 1 month received roxithromycin for 11 days (150 mg twice daily). Bi-weekly controls of plasma cyclosporin concentrations and creatinine levels were carried out before, during and after roxithromycin treatment. A slight nonsignificant rise in cyclosporin concentrations was observed, but creatinine levels remained stable during roxithromycin treatment. Values of cyclosporin concentrations diminished after withdrawal of roxithromycin. Cyclosporin dosage adjustment was not necessary. There was a minor pharmacokinetic interaction, which can be considered safe for the usual therapeutic dosage of roxithromycin used.

摘要

环孢素是一种常用于移植患者的免疫抑制剂。它可被细胞色素P450系统积极代谢,与由同一系统代谢的药物之间的相互作用是可预测的。这一点尤为重要,因为环孢素的治疗指数较低,且其肾毒性与浓度相关。罗红霉素是一种新型、耐受性良好且相互作用较弱的大环内酯类药物,它与环孢素使用细胞色素P450系统的同一种同工酶。为了评估其在临床实践中的相互作用潜力,8名接受环孢素治疗至少1个月的心脏移植受者接受了11天的罗红霉素治疗(每日两次,每次150毫克)。在罗红霉素治疗前、治疗期间和治疗后,每两周对血浆环孢素浓度和肌酐水平进行一次监测。观察到环孢素浓度有轻微但无统计学意义的升高,但在罗红霉素治疗期间肌酐水平保持稳定。停用罗红霉素后,环孢素浓度值下降。无需调整环孢素剂量。存在轻微的药代动力学相互作用,对于所使用的罗红霉素常规治疗剂量而言,可认为是安全的。

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