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目的描述卡培他滨在血浆、乳腺肿瘤组织和正常组织中向氟脲嘧啶转化的药物动力学过程。方法27名乳腺癌化疗患者口服卡培他滨1 255 mg·m-2,同步采集血浆、肿瘤组织和相邻正常组织样品,并用HPLC法测定卡培他滨和5-FU的浓度。使用自建的药物动力学模型拟合卡培他滨和5-FU的药时曲线,并利用拟合参数计算血浆和乳腺组织中卡培他滨和5-FU的组织分布因子,以及卡培他滨向5-FU的转化率。结果卡培他滨在肿瘤组织中的组织分布因子(AUCTumor/AUCplasma)为0.637 1,正常组织中的组织分布因子(AUCH-tissue/AUCplasma)为0·851 4;5-FU在乳腺肿瘤的组织分布因子AUCTumor/AUCplasma为3.992 6,正常组织的组织分布因子AUCH-tissue/AUCplasma为2.438 0。卡培他滨向5-FU的转化率在肿瘤、邻近正常组织和血浆中分别为1.026、0.489 5和0.163。结论血浆、乳腺肿瘤组织和相邻正常组织的药时曲线拟合对卡培他滨转化为5-FU及5-FU消除过程进行了较好的描述。卡培他滨在血浆、乳腺肿瘤组织和相邻正常组织中的分布较为接近,其活性代谢产物5-FU在肿瘤组织中分布为血浆的10·14倍,为正常组织的3·41倍。卡培他滨在肿瘤组织中向5-FU的转化率较高。
Objective To describe the pharmacokinetics of capecitabine in the conversion of fluorouracil to plasma, breast tumor tissue and normal tissues. METHODS: Twenty-seven breast cancer patients received capecitabine 1 255 mg · m-2. Plasma samples, tumor tissues and adjacent normal tissues were collected simultaneously. The concentrations of capecitabine and 5-FU were determined by HPLC. The pharmacokinetic model of Capecitabine and 5-FU was used to fit the pharmacokinetic model and the distribution parameters of capecitabine and 5-FU in plasma and mammary gland were calculated by fitting parameters. His rate of conversion to 5-FU. Results The AUCTumor / AUCplasma in the tumor tissue was 0.6371, the AUCH-tissue / AUCplasma in the normal tissue was 0.851 4. The expression of 5-FU in the tissue of the breast tumor The distribution factor AUCTumor / AUCplasma was 3.992 6, the normal tissue tissue distribution factor AUCH-tissue / AUCplasma 2.438 0. The conversion of capecitabine to 5-FU was 1.026, 0.4889 and 0.163 in tumors, adjacent normal tissues and plasma, respectively. Conclusion The time-curve fitting of capecitabine to 5-FU and 5-FU in plasma, breast tumor and adjacent normal tissues is well described. The distribution of capecitabine in plasma, breast tumor tissues and adjacent normal tissues was close, and the active metabolite 5-FU was 10.4 times of the plasma in tumor tissues, which was 3.41 times of normal tissues. Capecitabine has a higher rate of conversion to 5-FU in tumor tissue.