肾移植术后糖皮质激素和他克莫司的药代动力学相互作用

doi:10.5246/jcps.2019.04.026

摘要/Abstract

摘要：

糖皮质激素由于是CYP3A4和P-gp的诱导剂与他克莫司(tacrolimus, TAC)存在相互作用。但是, 目前研究中的糖皮质激素剂量均为低剂量而非冲击剂量。本研究回顾性的研究63名肾移植术后患者, 根据患者服用的糖皮质激素剂量进行分组: 500 mg (术后1–3天), 30 mg (术后4–10天), 25 mg (术后11–17天), 20 mg (术后18–24天), 15 mg (术后25–31天), 10 mg (术后32–60天) 和10 mg (术后61–90天)。我们每日详细记录患者从手术至术后90天的患者检验和用药信息。研究发现: 术后3个月内, 不同糖皮质激素剂量下TAC的血药浓度无显著性差异, 但是随着糖皮质激素的剂量减低, TAC的平均每日剂量显著性降低。同时, 术后1–4天内, TAC每日的剂量没有变化, 但是当糖皮质激素的剂量由500 mg减为30 mg时, TAC的浓度显著降低。本研究验证了低剂量的糖皮质激素对TAC的诱导效应, 同时发现高剂量糖皮质激素和他克莫司合用时, 糖皮质激素可能起到相关作用, 为竞争性底物效果。因此在肾移植术后受者的糖皮质激素剂量发生变化时, 监测TAC的血药浓度是有必要的。

关键词: 相互作用, 他克莫司, 糖皮质激素, 药代动力学, CYP3A4

Abstract:

There is an interaction between tacrolimus (TAC) and glucocorticoids where glucocorticoids is a known CYP3A4 and P-gp inducer. However, the dose of glucocorticoids reported is low but not pulse therapy. We retrospectively studied 63 renal transplant recipients receiving TAC after transplantation. All the patients were classified as 500 mg (POD 1–3), 30 mg (POD 4–10), 25 mg (POD 11–17), 20 mg (POD 18–24), 15 mg (POD 25–31), 10 mg (POD 32–60) and 10 mg (POD 61–90). We recorded daily data for each patient from the day of transplantation until POD 90. There was no difference in TAC blood levels within the 3 months after transplantation in the glucocorticoids groups. However, the average daily dose of TAC was significantly lower by weekly reductions of 5 mg dose. The TAC daily dose was not changed from POD 1–4, but the blood concentrations of TAC were significantly lower after the glucocorticoid dose was changed from 500 mg to 30 mg. We demonstrated the induction effect of low-dose glucocorticoids on TAC in renal transplant recipients, and found that the high-dose of glucocorticoids might play a role in substrate competition. We proposed that monitoring of the blood concentrations of TAC was needed when the glucocorticoid dose was changed in the patient undergoing renal transplantation.

Key words: Interaction, Tacrolimus, Glucocorticoids, Pharmacokinetic, CYP3A4

中图分类号:

R969.1

Supporting:

杨辉, 胡小鹏, 杨晓勇, 刘航, 任亮, 王玮, 刘丽宏, 张小东. 肾移植术后糖皮质激素和他克莫司的药代动力学相互作用[J]. 中国药学(英文版), 2019, 28(4): 257-263.

Hui Yang, Xiaopeng Hu, Xiongyong Yang, Hang Liu, Liang Ren, Wei Wang, Lihong Liu, Xiaodong Zhang. Pharmacokinetic interaction between glucocorticoids and tacrolimus after renal transplantation[J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(4): 257-263.

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