In vitro and in vivo pharmacokinetic and pharmacodynamic study of MBRI-001, a deuterium-substituted plinabulin derivative as a potent anti-cancer agent |
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| Authors: | Mingxu Ma Jianchun Zhao Hejuan Cheng Mengyan Deng Zhongpeng Ding Yingwei Hou Feng Li Guifang Dou Wenbao Li |
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| Institution: | 1. School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China;2. Innovation Center for Marine Drug Screening and Evaluation, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China;3. Marine Biomedical Research Institute of Qingdao, Qingdao 266071, China;4. Institute of Transfusion Medicine, Academy of Military Medical Sciences, Beijing 100850, China |
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| Abstract: | MBRI-001 was demonstrated preliminary better pharmacokinetics and antitumor effects than that of plinabulin in vivo. In this approach, we further carried out systematic pharmacokinetic and pharmacodynamic study of MBRI-001 in vitro and in vivo. MBRI-001 was tested stable in rat plasma and more stable in liver microsomes than plinabulin in vitro. In vivo, MBRI-001 could be distributed rapidly and widely in various tissues, especially the concentration of MBRI-001 in lung was remarkably higher than other tissues. Excretion study indicated that MBRI-001 might been decomposed and excreted as metabolites. Additionally, the combination treatment of MBRI-001 and gefitinib revealed better antitumor inhibition rate than monotherapy in vivo. Therefore, we suggest that MBRI-001 could be developed as a promising anti-cancer agent in near future. |
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| Keywords: | MBRI-001 Pharmacokinetics Pharmacodynamics Combination treatment Anticancer agent |
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