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血液透析与伊马替尼:1例转移性胃肠间质瘤患者的血药浓度、疗效及耐受性——病例报告

Hemodialysis and imatinib: Plasma levels, efficacy and tolerability in a patient with metastatic GIST - Case report.

作者信息

De Luca Ida, Miliziano Daniela, Guerra Giulia, Colombo Roberto, Morosi Carlo, Sposito Carlo, Fiore Marco, Venturelli Elisabetta, Sangalli Claudia, Casali Paolo G, Cavalleri Adalberto, Fumagalli Elena

机构信息

Fondazione IRCCS Istituto Nazionale dei Tumori, Oncologia medica 2 Tumori mesenchimali dell'adulto, Milan, Italy.

Fondazione IRCCS Istituto Nazionale dei Tumori, s.c. Epidemiologia e Prevenzione, Milan, Italy.

出版信息

Heliyon. 2024 Mar 27;10(7):e28494. doi: 10.1016/j.heliyon.2024.e28494. eCollection 2024 Apr 15.

Abstract

PURPOSE

To study plasma levels, efficacy and tolerability of imatinib in a patient affected by metastatic GIST treated with oral Imatinib and undergoing hemodialysis.

PATIENTS AND METHODS

The patient suffered from metastatic GIST to the liver having a mutation of exon 9 of KIT. He was on hemodialysis and received first-line treatment with imatinib 400 mg/day.

RESULTS

The overall mean plasma level of imatinib was 1875,4 ng/ml pre-dialysis, 1553,0 ng/ml post-dialysis and 1998,1 ng/ml post-24h. In red blood cells the overall mean level of imatinib was 619,5 ng/ml pre-dialysis, 484,9 ng/ml post-dialysis and 663,1 ng/ml post-24h. The plasma level of nor-imatinib/imatinib was 16,2% pre-dialysis, 15,6% post-dialysis and 16,4% post-24h. Comparing our findings regarding levels of imatinib in plasma and RBC, we found a statistically significant difference between pre-dialysis and post-dialysis (respectively p < 0,001 and p = 0,002), post-dialysis and post-24h (both p < 0,001), pre-dialysis and post-24h (respectively p = 0.035 and p = 0,042). Ultimately, regarding nor-imatinib/imatinib in plasma, we did not find any statistically significant difference between pre-dialysis and post-dialysis (p = 0,091), post-dialysis and post-24h (p = 0,091), pre-dialysis and post-24h (p = 0.903). Currently the patient is receiving oral imatinib 400 mg/day with radiological evidence of response.

CONCLUSION

In this case, hemodialysis did not affect significantly imatinib plasma levels. The statistically significant difference between pre- and post-dialysis can be explained by the fact that dialysis may likely contribute to a small portion of the normal metabolism of imatinib. The evaluation of imatinib levels in RBC and of its main metabolite in plasma also suggests that hemodialysis did not affect other aspects of the elimination of the drug.

摘要

目的

研究伊马替尼在接受口服伊马替尼治疗且正在进行血液透析的转移性胃肠道间质瘤(GIST)患者中的血浆水平、疗效和耐受性。

患者与方法

该患者患有肝脏转移性GIST,存在KIT基因第9外显子突变。他正在接受血液透析,并接受伊马替尼400mg/天的一线治疗。

结果

伊马替尼的总体平均血浆水平在透析前为1875.4ng/ml,透析后为1553.0ng/ml,透析后24小时为1998.1ng/ml。红细胞中伊马替尼的总体平均水平在透析前为619.5ng/ml,透析后为484.9ng/ml,透析后24小时为663.1ng/ml。去甲伊马替尼/伊马替尼的血浆水平在透析前为16.2%,透析后为15.6%,透析后24小时为16.4%。比较我们关于伊马替尼在血浆和红细胞中的水平的研究结果,我们发现透析前和透析后之间存在统计学显著差异(分别为p<0.001和p = 0.002),透析后和透析后24小时之间(均为p<0.001),透析前和透析后24小时之间(分别为p = 0.035和p = 0.042)。最终,关于血浆中的去甲伊马替尼/伊马替尼,我们在透析前和透析后之间未发现任何统计学显著差异(p = 0.091),透析后和透析后24小时之间(p = 0.091),透析前和透析后24小时之间(p = 0.903)。目前该患者正在接受伊马替尼400mg/天口服治疗,有影像学反应证据。

结论

在这种情况下,血液透析对伊马替尼血浆水平没有显著影响。透析前和透析后之间的统计学显著差异可以通过透析可能对伊马替尼的正常代谢有一小部分贡献这一事实来解释。对红细胞中伊马替尼水平及其血浆中主要代谢物的评估也表明血液透析未影响药物消除的其他方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a22/11002597/2b4f213bff56/gr1.jpg

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