[Biopharmaceutical studies on molecular mechanisms of membrane transport].
[Biopharmaceutical studies on molecular mechanisms of membrane transport].
复制标题
膜转运分子机制的生物制药研究。
DOI：
--
复制
发表时间：
2002
期刊：
影响因子：
--
通讯作者：
A. Tsuji
中科院分区：
文献类型：
--
作者：
A. Tsuji
通过将转运蛋白介导的或受体介导的运输过程中的生理基础的药代动力学模型，我们成功地定量预测β-内酰胺类抗生素，胰岛素，喷他佐辛，喹诺酮类抗菌药物，inperizone和地高辛的血浆和组织浓度。作者在转运蛋白介导的药代动力学方面的研究主要集中在寡肽转运蛋白、单羧酸转运蛋白、阴离子反向转运蛋白、有机阴离子转运蛋白、有机阳离子/肉毒碱转运蛋白（OCTNs）以及ATP结合盒转运蛋白P-糖蛋白和MRP 2等药物转运蛋白的分子和功能特征。我们已经成功地证明了这些转运蛋白在肠和肾上皮细胞、肝细胞和形成血脑屏障的脑毛细血管内皮细胞中药物的流入和/或流出中起重要作用。在系统性肉毒碱缺乏症（SCD）小鼠模型--幼年内脏脂肪变性（jvs）小鼠中发现了OCTN 2基因的突变，并在人类SCD患者中发现了多种突变类型，表明OCTN 2是一种重要的生理性肉毒碱转运蛋白。有趣的是，OCTN以钠依赖性方式转运肉毒碱，而各种阳离子药物以钠非依赖性方式转运肉毒碱。OCTN被认为是将肉毒碱摄取到组织细胞中以及消除细胞内有机阳离子药物的多功能转运蛋白。
By incorporating the transporter-mediated or receptor-mediated transport process in physiologically based pharmacokinetic models, we succeeded in the quantitative prediction of plasma and tissue concentrations of beta-lactam antibiotics, insulin, pentazocine, quinolone antibacterial agents, and inaperizone and digoxin. The author's research on transporter-mediated pharmacokinetics focuses on the molecular and functional characteristics of drug transporters such as oligopeptide transporter, monocarboxylic acid transporter, anion antiporter, organic anion transporters, organic cation/carnitine transporters (OCTNs), and the ATP-binding cassette transporters P-glycoprotein and MRP2. We have successfully demonstrated that these transporters play important roles in the influxes and/or effluxes of drugs in intestinal and renal epithelial cells, hepatocytes, and brain capillary endothelial cells that form the blood-brain barrier. In the systemic carnitine deficiency (SCD) phenotype mouse model, juvenile visceral steatosis (jvs) mouse, a mutation in the OCTN2 gene was found. Furthermore, several types of mutation in human SCD patients were found, demonstrating that OCTN2 is a physiologically important carnitine transporter. Interestingly, OCTNs transport carnitine in a sodium-dependent manner and various cationic drugs transport it in a sodium-independent manner. OCTNs are thought to be multifunctional transporters for the uptake of carnitine into tissue cells and for the elimination of intracellular organic cationic drugs.
DOI：
10.1006/bbrc.1998.9298
发表时间：
1998-09-18
影响因子：
3.1
作者：
Balimane, PV;Tamai, I;Sinko, PJ
通讯作者：
Sinko, PJ