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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Wang, Xianqin Wang, Shuanghu Lin, Feiyan Zhang, Qingwei Chen, HuiLing Wang, Xianchuan Wen, Congcong Ma, Jianshe Hu, Lufeng |
| Description | Country affiliation: China Author Affiliation: Wang X ( Analytical and Testing Center, Wenzhou Medical University, 325035 Wenzhou, China.); Wang S ( The Laboratory of Clinical Pharmacy, People's Hospital of Lishui City, 323000 Lishui, China.); Lin F ( The First Affiliated Hospital of Wenzhou Medical University, 325035 Wenzhou, China.); Zhang Q ( Shanghai Institute of Pharmaceutical Industry, 200437 Shanghai, China.); Chen H ( College of Physics and Electronic Information Engineering, Wenzhou University, 325035 Wenzhou, China.); Wang X ( Analytical and Testing Center, Wenzhou Medical University, 325035 Wenzhou, China.); Wen C ( Analytical and Testing Center, Wenzhou Medical University, 325035 Wenzhou, China.); Ma J ( Analytical and Testing Center, Wenzhou Medical University, 325035 Wenzhou, China.); Hu L ( The First Affiliated Hospital of Wenzhou Medical University, 325035 Wenzhou, China. Electronic address: hulufeng79@sina.com.) |
| Abstract | Cabozantinib (XL184) is a novel small molecule inhibitor of receptor tyrosine kinases (RTKs) targeted at mesenchymal-epithelial transition factor (MET). In order to study the pharmacokinetics and tissue distribution in rat, a specific ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed with midazolam as internal standard. The calibration curves in plasma and tissues were linear in the range of 5-5000ng/mL (r(2)>0.99). The recoveries were better than 80.4% and matrix effects ranged from 96.9% to 105.1%. Then, the developed UPLC-MS/MS method was applied to determine the concentration of XL184 in blood and tissues. The pharmacokinetics of four different dosages (iv 5, 10mg/kg and ig 15, 30mg/kg) revealed that XL184 was eliminated slowly, the t1/2 was longer than 10h and the absolute bioavailability was 25.6±8.3%. The concentration distribution of XL184 in tissues was liver>lung>kidney>spleen>heart. Based on the concentration-time of XL184 in tissues, a BP-ANN distribution model was developed with good performance, and can be used to predict the concentration of XL184 in tissues. |
| File Format | HTM / HTML |
| ISSN | 15700232 |
| Volume Number | 983-984 |
| e-ISSN | 1873376X |
| Journal | Journal of Chromatography B |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2015-03-01 |
| Publisher Place | Netherlands |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Analytical Chemistry Anilides Pharmacokinetics Chromatography, High Pressure Liquid Methods Pyridines Tandem Mass Spectrometry Administration & Dosage Blood Chemistry Animals Calibration Drug Stability Liver Metabolism Midazolam Neural Networks (computer) Rats Rats, Sprague-dawley Reproducibility Of Results Tissue Distribution Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine Analytical Chemistry Clinical Biochemistry Biochemistry |
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