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首页> 外文期刊>薬物動態 >Effect of Biliary Excretion on the Pharmacokinetics of Pitavastatin (NK-104) in Dogs
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Effect of Biliary Excretion on the Pharmacokinetics of Pitavastatin (NK-104) in Dogs

机译：胆汁排泄对犬斗狗（NK-104）的药代动力学的影响

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The disposition of pitavastatin and pitavastatin lactone, which are mutually converted in the circulatory system, was investigated after intravenous adminstration of pitavastatin in dogs equipped with chronic bile-duct catheters.The plasma concentration of pitavastatin declined three-exponentially after dosing in the dogs with both diverted and non-diverted bile-flow. The terminal elimination half-life (T_(1/2) of pitavastatin in the diverted and non-diverted conditions was 3.12 and 5.01 hr, and that of pitavastatin lactone 4.50 and 7.23 hr, respectively. The diverted bile-flow decreased the AUC_(0-24hr) for pitavastatin and its lactone to 66 and64%, respectively.In the dogs with the diverted bile-flow, 56.1% and 4.2% of the dose was recovered in the bile as pitavasta tin and its lactone, respectively.t eh biliary clearance (CL_b) of pitavastatin and its lactone was 32.5 and 6.8 mL/min, respectively, and the CL_b of pitavastatin was about 4.8-fold that of its lactone.In the dogs whose bile-flow was not diverted, the cumulative biliary excretion of pitavastatin and its lactone was estimated from the AUC_(0-24 hr) and CL_b of both forms of pitavastatin. The estimated amount was increased by 46% compared with that in the dogswith the diverted bile-flow. This indicates that the increase reflects the actual contribution of the enterohepatic circulation.
机译：在配备慢性胆管导管的猪伐他汀的静脉伴素静脉施用后，研究了匹伐他汀和匹伐他汀内酯的探测器，其在循环系统中进行了研究，捕获胆汁导管的静脉抗刺激素血浆浓度在用两者携带犬犬中的三指数下降了三次 - 指数转移和非转移的胆汁流动。转移和非转移条件下的匹伐他汀的终端消除半衰期（T_（1/2）为3.12和5.01小时，分别为匹伐他汀内酯4.50和7.23小时。转移的胆汁流量减少了AUC_（ 0-24HR）对于岩伐他汀及其内酯分别为66〜64％。在狗的胆汁流动的狗中，分别在胆汁酸锡锡及其内酯中回收56.1％和4.2％的剂量。 Pitavastatin及其内酯的胆道间隙（Cl_B）分别为32.5和6.8ml / min，匹伐他汀的CL_B为其内酯的4.8倍。在胆汁流动未转移的狗，累积胆汁排泄从两种形式的匹伐他汀的AUC_（0-24小时）和CL_B估计了匹伐他汀及其内酯。与转向的胆汁流动的狗言相比，估计量增加了46％。这表明增加了增加反映肠内循环的实际贡献。

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