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首页> 外文期刊>Life sciences >The pharmacokinetic change of lidocaine by catecholamines using isolated perfused rat liver (IPRL).
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The pharmacokinetic change of lidocaine by catecholamines using isolated perfused rat liver (IPRL).

机译：儿茶酚胺使用离体灌流大鼠肝脏（IPRL）引起的利多卡因药代动力学变化。

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摘要

We hypothesized that changes in the pharmacokinetics of lidocaine might reveal changes in portal circulation induced by catecholamines. Isolated perfused rat liver (IPRL) was selected as an experimental model, since experimental conditions in this model could be regulated. The liver was perfused with a recirculating system at a constant flow rate of 20 ml/min. Two milligrams of lidocaine was administered along with one of three drugs, dopamine, norepinephrine or adenosine triphosphate. The fractional transfer rate constants, k21 and k12, from medium to liver and liver to medium, respectively, and ke, the elimination rate constant, were calculated using a two-compartment model with the SAAM II program. Curves of decay of lidocaine from the recirculating medium consisted of a fast and a slow component. Norepinephrine and high-dose dopamine significantly increased k12, while low-dose dopamine significantly increased k21 and ke compared with control values. Thus, norepinephrine and high-dose dopamine increased lidocaine transfer rate from liver to medium, while low-dose dopamine increased the transfer rate from medium to liver and the rate of elimination from liver. These findings suggest that norepinephrine and high-dose dopamine inhibit hepatic drug uptake and that low-dose dopamine improves uptake in IPRL.
机译：我们假设利多卡因的药代动力学变化可能揭示儿茶酚胺诱导的门脉循环变化。选择离体灌流大鼠肝脏（IPRL）作为实验模型，因为可以调节该模型中的实验条件。以20 ml / min的恒定流速向肝脏灌注再循环系统。服用了2毫克的利多卡因以及三种药物中的一种，即多巴胺，去甲肾上腺素或三磷酸腺苷。使用带有SAAM II程序的两室模型，分别计算了从培养基到肝脏和从肝脏到培养基的分数转移速率常数k21和k12，以及消除速率常数ke ke。利多卡因从循环介质中的衰减曲线由快和慢组成。与对照组相比，去甲肾上腺素和高剂量多巴胺显着增加k12，而低剂量多巴胺显着增加k21和ke。因此，去甲肾上腺素和大剂量多巴胺提高了利多卡因从肝脏到培养基的转移速率，而小剂量多巴胺增加了从中毒到肝脏的转移速率和从肝脏清除的速率。这些发现表明去甲肾上腺素和大剂量多巴胺会抑制肝药物的摄取，而小剂量多巴胺会改善IPRL的摄取。

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