- 著者
- Qubo Zhu Zhifang Liu Pei Li Zeneng Cheng
- 出版者
- 日本薬物動態学会 会長/日本薬物動態学会 DMPK編集委員長
- 雑誌
- Drug Metabolism and Pharmacokinetics (ISSN:13474367)
- 巻号頁・発行日
- pp.DMPK-13-RG-123, (Released:2014-02-11)
- 参考文献数
- 30
- 被引用文献数
- 9
Hypothesis: Simotinib Hydrochloride (SIM6802), which is a new epidermal growth factor receptor-tyrosine kinases inhibitor (EGFR-TKI), is often prescribed for cancer patients with comorbidities and has serious adverse effects gastrointestinal physiology. The drug-drug interactions (DDI) between simotinib and other drugs in combination and the underlying mechanism of its gastrointestinal toxicity remains unclear. We hypothesized that the DDI and the gastrointestinal toxicity of simotinib was related to its effects on the permeability of intestine. Methods: To determine the intestinal absorption ability, pharmacokinetic studies and in situ loop assay were used. The intestinal permeability was measured by Caco-2 transwell model. Real time PCR and western blots were applied to detecting the expression changes of cell junction genes. Results: Our research demonstrated that simotinib upregulated the absorption of cefaclor, valaciclovir and acyclovir. The increase of non-selective absorption was caused by the low expression of cell junction gene afadin-6 and the increasing of paracellular permeability in intestinal epithelial cells after simotinib treatment. Conclusion: These findings revealed that simotinib upregulated intestinal absorption by increasing the paracellular permeability of intestinal epithelial cells. Our research provides theoretical bases for better formulation of EGFR-TKIs to alleviate adverse gastrointestinal effects and also provides guidance for clinical administration of simotinib.
- 著者
- Yan ZHANG Xiaoyan HUANG Wenfang LIU Zeneng CHENG Chuanpin CHEN Lihui YIN
- 出版者
- (社)日本分析化学会
- 雑誌
- Analytical Sciences (ISSN:09106340)
- 巻号頁・発行日
- vol.29, no.10, pp.985-990, 2013-10-10 (Released:2013-10-10)
- 参考文献数
- 34
- 被引用文献数
- 3 24
Illegal chemicals, which could cause unpredictable side effects, may be added into traditional Chinese medicine (TCM) for a rapid healing effect. In this report, a surface-enhanced Raman scattering (SERS) analysis method for five kinds of illegally added drugs (rosiglitazone maleate, phenformin hydrochloride, metformin hydrochloride, pioglitazone hydrochloride and sibutramine hydrochloride) in Chinese traditional patent medicine (CTPM) has been demonstrated, including simultaneous detections of drug mixtures with CTPM. Silver colloidal, prepared by a sodium citrate reaction, was used as a SERS substrate. The optimum pH condition for each drug has also been explored because of its combined effect on protonation, surface charge, repulsion of an analyte and nanoparticles. Furthermore, the simultaneous detection of two or three kinds of these chemicals has been carried out. Characteristic peaks are employed for qualitative analysis. This is the first research using SERS for the analysis of drug mixtures in CTPM without any separation process.