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延长微透析采样在卡铂治疗的癌症患者中的应用。

Application of prolonged microdialysis sampling in carboplatin-treated cancer patients.

作者信息

Konings Inge R H M, Engels Frederike K, Sleijfer Stefan, Verweij Jaap, Wiemer Erik A C, Loos Walter J

机构信息

Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.

出版信息

Cancer Chemother Pharmacol. 2009 Aug;64(3):509-16. doi: 10.1007/s00280-008-0898-0. Epub 2008 Dec 20.

Abstract

PURPOSE

To better understand the mechanisms underlying (in)sensitivity of tumors to anticancer drugs, assessing intra-tumor drug pharmacokinetics (PKs) could be important. We explored the feasibility of microdialysis in tumor tissue for multiple days in a clinical setting, using carboplatin as model drug.

METHODS

Plasma and microdialysate samples from tumor and adipose normal tissues were collected up to 47 h after dosing in eight carboplatin-treated patients with an accessible (sub)cutaneous tumor.

RESULTS

Pharmacokinetics were evaluable in tumor tissue in 6/8 patients and in adipose normal tissue in 3/8 patients. Concentration-time curves of unbound platinum in both the tissues followed the pattern of the curves in plasma, with exposure ratios of tissue versus plasma ranging from 0.64 to 1.46.

CONCLUSIONS

Microdialysis can be successfully employed in ambulant patients for multiple days, which enables one to study tissue PK of anticancer drugs in normal and malignant tissues in more detail.

摘要

目的

为了更好地理解肿瘤对抗癌药物(不)敏感的潜在机制,评估肿瘤内药物药代动力学(PKs)可能很重要。我们以卡铂为模型药物,探讨了在临床环境中对肿瘤组织进行多天微透析的可行性。

方法

在8例接受卡铂治疗且有可触及(皮下)肿瘤的患者给药后47小时内,收集肿瘤组织和脂肪正常组织的血浆及微透析液样本。

结果

6/8例患者的肿瘤组织和3/8例患者的脂肪正常组织中的药代动力学可评估。两种组织中游离铂的浓度-时间曲线均遵循血浆曲线模式,组织与血浆的暴露比为0.64至1.46。

结论

微透析可成功应用于门诊患者,这使得人们能够更详细地研究抗癌药物在正常组织和恶性组织中的组织PK。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0bd/2691802/0638c674a126/280_2008_898_Fig1_HTML.jpg

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