王广基
致力于应用药物代谢动力学与代谢组学等前沿科学相结合的研究手段,建立新型中药及方剂复杂体系药物代谢动力学研究及药效学整体评价体系,为中药现代化研究开辟全新的研究思路与方法。
个性化签名
- 姓名:王广基
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学术头衔:
博士生导师
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学科领域:
岩土力学
- 研究兴趣:致力于应用药物代谢动力学与代谢组学等前沿科学相结合的研究手段,建立新型中药及方剂复杂体系药物代谢动力学研究及药效学整体评价体系,为中药现代化研究开辟全新的研究思路与方法。
王广基,博士、教授、博士生导师,中国药科大学副校长。1953年生,1977年9月毕业于中国药科大学,毕业后留校任教。1982年11月至1984年9月赴英国剑桥及瑞典卡罗琳斯卡医学院学习药物代谢动力学,回国后任讲师。1990年4月至91年4月,在澳大利亚昆士兰大学药学系,攻读博士学位,主攻方向药物代谢动力学。1991年4月至93年7月,在新西兰Otago大学药学院,攻读博士学位,主攻方向眼用制剂吸收动力学。1993年8月至95年10月,在新西兰Otago大学药学院,进行博士后研究,95年10月回国。现任中国药科大学副校长,科技部临床前药物代谢动力学研究平台主任(全国牵头人), 江苏省药物代谢动力学重点实验室主任,中国药学会应用药理专业委员会主任委员,中国药理学会药物代谢动力学专业委员会副主任委员,中国药理学会制药工业专业委员会副主任委员,江苏省药理学会常务理事兼副秘书长,国家药品食品监督管理局和江苏省药品审评专家, 国家自然科学基金委评审委员,国家人事部顾问委员会委员,《中国药理学报》,《亚洲药物代谢动力学杂志》,《中国药科大学学报》,《中国临床药理学与治疗学》,《亚洲临床药理学与治疗学》等核心学术期刊杂志编委等职,享受国务院特殊津贴。
曾主持国家科委“973”子项目、“863”重大专项、国家自然科学基金、国家新药基金等多项国家重点项目研究工作。作为全国牵头人,主持国家“863”重大专项“临床前药物代谢动力学关键技术及平台研究” (项目编号2003AA2Z3471),到帐经费2090万元,该项目已于2005年12月顺利通过了由国家科技部组织的专家组验收,由十一名院士组成的专家组对该项目所取得的研究成果给予了高度评价,认为其对我国药物代谢动力学研究水平的整体提高及实现与国际接轨起到了极大的推动作用。
近三年来先后完成了盐酸关附甲素、86017、DDPH、大黄酸、豆腐果苷、人参皂苷Rg3等数十个I类创新药物的动物药物代谢动力学研究和多项II、IV药物的药物代谢动力学研究。共培养毕业研究生27名,其中博士10名,目前在读硕士24名,博士16名。近年来在国内外刊物上发表有关学术论文137篇,其中SCI收录47篇(其中5篇影响因子>3, 3篇影响因子>5),出版专著2部。荣获江苏省科技进步一等奖1项、三等奖1项。申请及获授权专利共11项。在创新药物药代动力学新理论与新模型研究、中药药物代谢动力学研究、药代药效结合等研究领域取得了突出成就,在国内外享有较高知名度,受邀成为Journal of Mass Spectrometry, Rapid Communications in Mass Spectrometry, Journal of Chromatography B, European Journal of Pharmaceutics and Biopharmaceutics等国际知名期刊的特约审稿人。现正致力于应用药物代谢动力学与代谢组学等前沿科学相结合的研究手段,建立新型中药及方剂复杂体系药物代谢动力学研究及药效学整体评价体系,为中药现代化研究开辟全新的研究思路与方法。
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5
王广基, Miao Chen, Guang-Ji Wang, Yong Diao, Rui-An Xu, Hai-Tang Xie, Xin-Yan Li, Jian-Guo Sun, Miao Chen, Jiangsu
R World J Gastroenterol July 14, 2005 Volume 11 Number 26,-0001,():
-1年11月30日
AIM: To investigate the effects of adeno-associated virus (AAV) mediated expression of human interferon-γ for gene therapy in experimental hepatic fibrosis in vitro and in vivo. METHODS: We constructed the recombinant AAV encoding human INF-γ (rAAV-INF-γ) and took the primary rat hepatic stellate cells and carbon tetrachloride induced rats as the experimental hepatic fibrosis model in vitro and in vivo. Immunocytochemistry analysis was used to reveal the expression of α-SMA, the marker protein expressed in hepatic stellate cells. The mRNA expression of TGF-β, TIMP-1, and MMP-13 were analyzed by RT-PCR method. In vivo study, the hydroxyproline content in liver and serum AST, ALT were also detected. RESULTS: In vitro study, AAV vector could mediated efficient expression of human INF-γ, which inhibit the activation of hepatic stellate cells, decrease the expression of α-SMA and mRNA of TIMP-1, TGF-β, with the MMP-13 unchanged. In vivo study, the histological examination revealed that rAAV-INF-γ could inhibit the progression of the hepatic fibrosis. In the rAAV-INF-γ induced group, the hydroxyproline content and serum AST, ALT level were decreased to 177±28μg/g wet liver, 668.5±140.0, 458.4±123.5U/L, compare with the fibrosis control group 236±31μg/g wet liver, 1019.1±276.3, 770.5±154.3U/L, respectively (P<0.01). mRNA expression of TIMP-1 in the rAAV-INF-γ induced rat liver was decreased while no significant change was observed in TGF-β and MMP-13.CONCLUSION: All these results indicated that rAAV-INF-γ has potential effects for gene therapy of hepatic fibrosis, which could inhibit the progression of hepatic fibrosis.
Adeno-associated virus, Interferon-γ, Hepatic stellate cells, Hepatic fibrosis
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【期刊论文】Pharmacokinetics of Guanfu Base I, an Active Metabolite of Guanfu Base A, in Rats
王广基, Xiaotian LI, Guangji WANG, * Sujun WANG, Jianguo SUN, and Jinghan LIU
Biol. Pharm. Bull. 28 (8) 1363-1365 (2005),-0001,():
-1年11月30日
A liquid chromatographic-mass spectrometric (LC-MS) method was developed and validated for determination of guanfu base I (GFI), and the pharmacokinetics of GFI in Sprague-Dawley rats was examined. The method was linear in the 0.05-20mg/ml concentration range (r=0.9994). The recovery of guanfu base I was more than 80%. The intraday and interday precision, expressed as the relative standard deviation (RSD), was generally good (<15%). After i.v. dosing, plasma GFI concentration declined in a bi-phasic manner with a terminal elimination half-life of 2.49h. The total plasma clearance values was 1.46l/h/kg. After oral dosing, the plasma GFI concentration reached a maximum within 0.5h. The absolute bioavailability of GFI was 71.31%.
guanfu base I, pharmacokinetics, LC-MS
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王广基, Qi ZHANG, Guang-ji WANG, Jian-guo SUN
Acta Pharmacol Sin 2004 Aug; 25 (8): 991-995,-0001,():
-1年11月30日
AIM: To study the pharmacokinetics of recombinant human basic fibroblast growth factor (rhbFGF) in rabbits and mice after iv and postocular administration, and the changes of rhbFGF in rabbits aqueous humor after postocular administration. METHODS: After iv or postocular administration three doses of rhbFGF in rabbits and mice, rhbFGF concentration in serum and rabbit aqueous humor was determined by enzyme-linked immunosorbent assay. RESULTS: Serum concentration-time data of rabbits after iv administration of rhbFGF 1, 2, and 4μg/kg were fitted to bi-exponential equations with half-lives of 0.9, 0.9, and 0.6min for T1/2α and 7, 8, and 4.7min for T1/2β. Plasma concentration-time data of mice after iv administration of rhbFGF 2.5, 5 and 10 μg/kg were fitted to biexponential equations with half-lives of 0.4, 0.6, and 0.9min for T1/2α and 6, 5, and 7min for T1/2β. The AUCs were linearly correlated to doses in both cases (rrabbit=0.997, rmouse=0.999). The serum concentrations of rhbFGF were very low, near to the background after postocular administration of 2 or 5μg/kg, in both rabbits and mice. The rhbFGF levels in rabbits aqueous humor were higher than control 8h postdose (P<0.01). CONCLUSION: rhbFGF within the examined doses had a linear pharmacokinetics in rabbits and mice. High concentration of rhbFGF was found in rabbits aqueous humor after postocular administration.
fibroblast growth factor 2, pharmacokinetics, enzyme-linked immunosorbent assay, aqueous humor, rabbits, mice
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王广基, Yongchuan Gu a, b, *, Guangji Wang a, J. Paul Fawcett b
Journal of Chromatography B, 801(2004)285-288,-0001,():
-1年11月30日
Astragaloside Ⅳ (AGS-Ⅳ) is an active constituent of Radix Astragali used in many Traditional Chinese Medicines. This paper describes a sensitive and specific assay for the quantitation of AGS-Ⅳ in rat plasma. After solid phase extraction (SPE), samples were analyzed by liquid chromatography electrospray ionization mass spectrometry using a reversed-phase C18 column. The assay was linear in the range 1-500ng/ml with a limit of detection of 0.5ng/ml. The recovery was 92.5% and within-day and between-day precision were 3.7-6.0 and 2.8-9.8%, respectively. The assay was applied to a pharmacokinetic study in rat after a single oral dose. The drug was rapidly absorbed and subsequently eliminated according to a biphasic concentration-time curve.
Astragaloside Ⅳ
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王广基, YANG Hai-Tao, WANG Guang-Ji
Acta Pharmacol Sin 2003 Dec; 24 (12): 1185-1191,-0001,():
-1年11月30日
AIM: The characteristics of transepithelial transport and uptake of CPU-86017 {[7-(4-chlorbenzyl)-7,8,13,13-tetrahydroberberine chloride, CTHB]}, a new antiarrhythmia agent and a new derivative of berberine, were investigated on epithelial cell line (Caco-2) to further understand the absorption mechanism of berberine and its derivatives. METHODS: Caco-2 cell was used. RESULTS: 1) The permeability coefficient from the apical (AP) to basolateral (BL) of CPU-86017 was approximately 5 times higher than that from BL-to-AP transport. The effects of a P-glycoprotein (P-gp) inhibitorcyclosporin A, some surfactants, and lower pH on the transepithelial transport of CPU-86017 were also observed. Cyclosporine A at 7.5mg/L had no effect on the transepithelial electrical resistance (TEER); an about 4-fold enhancement on the transepithlial transport of CPU-86017 was observed. Some surfactants (sodium citrate, sodium deoxycholate, and sodium dodecyl sulfate) at 100μmol/L and low pH (pH=6.0) induced a reversible decrease of TEER; enhancements of the transepithelial transport of CPU-86017 were also observed with some surfactants; 2) In the process of uptake of CPU-86017, the initial uptake rates of CPU-86017 were saturable with a Vmax of (250±39) μg•min-1•g-1 (protein) and Km of (0.90±0.12)mmol/L. This process was enhanced by cyclosporine A (7.5mg/L) with a Vmax of (588±49)μg•min-1•g-1 (protein) and Km (0.42±0.08)mmol/L. CONCLUSION: Some surfactants and P-gp inhibitors can be considered as enhancers of its transepithelial transport and uptake.
CPU-86017, berberine, Caco-2 cell, cyclosorine A, sodium dodecylsulfate, doldium citrate, sodium deoxycholate
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