终末期肾病患者中克拉霉素与地高辛的相互作用。

Hirata S, Izumi S, Furukubo T, Ota M, Fujita M, Yamakawa T, Hasegawa I, Ohtani H, Sawada Y

Department of Pharmacy Service, Shirasagi Hospital, Osaka, Japan.

Int J Clin Pharmacol Ther. 2005 Jan;43(1):30-6. doi: 10.5414/cpp43030.

OBJECTIVE

To report a significant increase in the serum levels of digoxin associated with the use of clarithromycin in six patients undergoing renal replacement therapy.

CASE SUMMARY

All six patients were males with end-stage renal disease and in need of renal replacement therapy. Four patients were anuric. The mean age was 78.8 +/- 5.8 (66-83) years. All patients except one, who was treated by hemofiltration, were treated by hemodialysis. All patients except one, who had been treated with metildigoxin (0.35 mg/week), were also taking digoxin (0.375 mg/week). Clarithromycin was administered at a dose of 200-400 mg/day for the treatment of bronchitis in all patients. The concomitant administration of clarithromycin increased serum digoxin levels from 1.8-4.0-fold in all cases. In two of six cases, a high probability of digoxin intoxication and suspicion of digoxin intoxication was evident. In three of six cases, serum digoxin levels increased within 12 days after the co-administration of clarithromycin, while in the other three cases, serum digoxin levels were increased 53-190 days after the administration of clarithromycin.

CONCLUSION

The simultaneous administration of clarithromycin caused an increase in digoxin levels in six patients undergoing renal replacement therapy. The increase in the serum digoxin can be attributed to the inhibition of P-glycoprotein in the intestine and/or bile capillary rather than the kidney by clarithromycin since renal function was dramatically impaired, and four of the patients were anuric. The issue of why serum digoxin levels were increased so late in three patients undergoing renal replacement is unclear. However, this interaction seemed to be clinically significant even in ESRD patients, whose renal function was highly impaired. The simultaneous use of digoxin and clarithromycin should be avoided even in patients undergoing renal replacement therapy whose renal function is impaired, since digoxin levels may increase unexpectedly.

目的

报告6例接受肾脏替代治疗的患者在使用克拉霉素后血清地高辛水平显著升高。

病例摘要

6例患者均为男性，患有终末期肾病，需要进行肾脏替代治疗。4例患者无尿。平均年龄为78.8±5.8（66 - 83）岁。除1例接受血液滤过治疗的患者外，其余患者均接受血液透析治疗。除1例曾接受甲地高辛（0.35 mg/周）治疗的患者外，其余患者均服用地高辛（0.375 mg/周）。所有患者均给予200 - 400 mg/天的克拉霉素治疗支气管炎。在所有病例中，克拉霉素与地高辛同时使用使血清地高辛水平升高了1.8 - 4.0倍。6例中有2例明显有地高辛中毒的高可能性且怀疑地高辛中毒。6例中有3例在克拉霉素与地高辛联合使用后12天内血清地高辛水平升高，而另外3例在克拉霉素给药后53 - 190天血清地高辛水平升高。

结论

克拉霉素与地高辛同时使用导致6例接受肾脏替代治疗的患者地高辛水平升高。血清地高辛水平升高可归因于克拉霉素对肠道和/或胆小管中P - 糖蛋白的抑制，而非对肾脏的抑制，因为患者肾功能严重受损，且4例患者无尿。3例接受肾脏替代治疗的患者血清地高辛水平为何在如此晚的时候升高尚不清楚。然而，即使在肾功能严重受损的终末期肾病患者中，这种相互作用似乎在临床上也具有重要意义。即使是肾功能受损的接受肾脏替代治疗的患者，也应避免同时使用地高辛和克拉霉素，因为地高辛水平可能会意外升高。