Potential elevation of tacrolimus trough concentrations with concomitant metronidazole therapy
Potential elevation of tacrolimus trough concentrations with concomitant metronidazole therapy
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DOI：
10.1345/aph.1e399
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发表时间：
2005-06-01
影响因子：
2.9
通讯作者：
Rogers, C
中科院分区：
文献类型：
--
作者：
Page, RL;Klem, PM;Rogers, C
目的：为了报告一个潜在的他克莫司升高肾移植受体后，加入甲硝唑的medicine regiments.CASE概要：一个24岁的白色男子状态后，生活相关的肾移植谁已经稳定在他克莫司4毫克，每天两次（谷浓度7-10毫微克/毫升）2个月和泼尼松20毫克，每天出现严重腹泻的诊所。粪便培养为艰难梭菌阳性，开始甲硝唑500 mg每日4次治疗。在甲硝唑治疗的第4天至第14天之间，患者的他克莫司谷浓度和血清肌酐水平分别升高至最大水平26.3 ng/mL和3.3 mg/dL（基线1.6-1.8 mg/dL）。他克莫司暂停一次给药，然后降至1 mg，每日两次。甲硝唑停药后两天，他克莫司谷浓度下降到9.4 ng/mL和血清肌酐2.3 mg/dL，他克莫司剂量增加到3 mg daily.Discussion：截至2005年4月15日，另一个案件已被报道，记录他克莫司浓度升高，除了甲硝唑。其机制可能与甲硝唑对CYP 3A 4和P-糖蛋白的抑制作用较弱有关。根据Naranjo概率量表，甲硝唑是这种不良反应的可能原因。结论：他克莫司与甲硝唑的共同管理可能会导致他克莫司浓度升高，可能导致他克莫司毒性。从业者应意识到这种潜在的相互作用，并密切监测他克莫司浓度和肾功能。
OBJECTIVE: To report the occurrence of a potential tacrolimus elevation in a renal transplant recipient after adding metronidazole to the medication regimen.CASE SUMMARY: A 24-year-old white man status post living-related renal transplant who had been stabilized on tacrolimus 4 mg twice daily (trough concentrations 7-10 ng/mL) for 2 months and prednisone 20 mg daily presented to the clinic with severe diarrhea. Stool cultures were positive for Clostridium difficile, and therapy with metronidazole 500 mg 4 times daily was initiated. Between days 4 and 14 of metronidazole therapy, the patient's tacrolimus trough concentration and serum creatinine level increased to maximum levels of 26.3 ng/mL and 3.3 mg/dL (baseline 1.6-1.8 mg/dL), respectively. Tacrolimus was withheld for one dose and then decreased to 1 mg twice daily. Two days after metronidazole discontinuation, tacrolimus trough concentrations dropped to 9.4 ng/mL and serum creatinine to 2.3 mg/dL, warranting a tacrolimus dose increase to 3 mg daily.DISCUSSION: As of April 15, 2005, one other case has been reported documenting an elevation in tacrolimus concentrations with the addition of metronidazole. The possible mechanism may be related to metronidazole's weak inhibition of CYP3A4 and, possibly, P-glycoprotein. According to the Naranjo probability scale, metronidazole was the probable cause of this adverse reaction.CONCLUSIONS: Coadministration of tacrolimus with metronidazole may result in elevated tacrolimus concentrations, possibly leading to tacrolimus toxicity. Practitioners should be aware of this potential interaction and closely monitor tacrolimus concentrations and renal function.