Clearance of fentanyl, alfentanil, methohexitone, thiopentone and ketamine in relation to estimated hepatic blood flow in several animal species:: Application to prediction of clearance in man
Clearance of fentanyl, alfentanil, methohexitone, thiopentone and ketamine in relation to estimated hepatic blood flow in several animal species:: Application to prediction of clearance in man
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DOI：
10.1211/0022357001774985
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发表时间：
2000-09-01
影响因子：
3.3
通讯作者：
Redke, F
中科院分区：
文献类型：
--
作者：
Björkman, S;Redke, F
我们用估计的肝血流量（Q（hep））作为评估动物清除率（CL）值和预测人清除五种麻醉剂：芬太尼、阿芬太尼、美索己酮、硫喷妥钠和氯胺酮。进一步的数据从文献中汇编，并根据需要进行实验补充。用异速生长种间定标法（Allometric interspecies scaling），根据三种不同的方法，估算了人体的血液清除率和游离清除率（CLu），并根据估算的药物肝提取率（CL/Q（hep））对三种不同方法的定标结果进行了评价。在大多数动物中，药物的清除率与估算的Q（hep）相当或低于估算的Q（hep）。然而，氯胺酮在家兔中显示出广泛的肝外清除。至少有一种方法成功预测了所有五种药物在人体中的清除率，而预测CLu通常失败。CL/Q（hep）的估计值未表明最佳方法的选择。阿芬太尼、硫喷妥钠和氯胺酮的稳态分布容积可以预测，清除率与Q（hep）的比较应用于评价动物的清除率数据，但估计肝脏提取率似乎对异速生长比例没有多大用处。氯胺酮作为麻醉剂在家兔中的使用值得怀疑，而芬太尼在猪中的使用、美索己酮在大鼠中的使用以及氯胺酮在大鼠和猪中的使用得到了药代动力学数据的充分支持。
We have used estimated hepatic blood flow (Q(hep)) as an aid to evaluate clearance (CL) values in animals and to predict clearance in man of five anaesthetic agents: fentanyl, alfentanil, methohexitone, thiopentone and ketamine.The disposition of methohexitone was determined in rats and that of ketamine in rats, rabbits and pigs. Further data were compiled from the literature and supplemented experimentally as needed. Allometric interspecies scaling, according to three different methods, was used to estimate blood clearance and unbound clearance (CLu) in man. The results of scaling according to the three different methods were evaluated in relation to estimated hepatic extraction ratio (CL/Q(hep)) of the drugs.In most animals the clearance of the drugs were comparable with or lower than estimated Q(hep). However, ketamine showed extensive extrahepatic clearance in rabbits. Prediction of clearance in man was successful by at least one method for all five drugs, while prediction of CLu generally failed. Estimates of CL/Q(hep) gave no indication as to the choice of the best method. Volume of distribution at steady state could be predicted for alfentanil, thiopentone and ketamine.Comparison of clearance with Q(hep) should be used to evaluate clearance data in animals, however estimation of hepatic extraction ratios appears to be of little use for allometric scaling. The use of ketamine as an anaesthetic agent in rabbits is questionable, while the use of fentanyl in pigs, methohexitone in rats and ketamine in rats and pigs is well supported by the pharmacokinetic data.