Jurica Jan, Kyr Michal, McCaskey Hadasova Eva, Tomandl Josef
Department of Pharmacology, Masaryk University, Brno, Czech Republic.
Neuro Endocrinol Lett. 2009;30 Suppl 1:92-5.
A "cocktail" of several substrates is frequently used to assess metabolic activity of multiple cytochrome P450 enzymes in one session. Some interactions among substrates can appear and may influence the rate of biotransformation of other ones. Our current work was aimed on the influence of tolbutamide on cytochrome P450-mediated metabolism of phenacetin and vice versa.
In the presented work, the biotransformation rates of phenacetin and tolbutamide (markers of rat CYP1A2 and CYP2C6/11 metabolic activities, respectively) administered either separately or both simultaneously were compared. The model of isolated perfused rat liver was used.
Phenacetin had no significant effect on tolbutamide hydroxylation. Tolbutamide addition to the perfusion medium significantly increased the rate of O-deethylation of phenacetin.
Some differences in the rate of P450-mediated metabolism can be observed when comparing assessment using combination of two model substrates with the common way (single marker administration). Due to these differences, results obtained by the mentioned methodologies might not be fully comparable.
通常使用几种底物的“鸡尾酒”来在一次实验中评估多种细胞色素P450酶的代谢活性。底物之间可能会出现一些相互作用，这可能会影响其他底物的生物转化速率。我们当前的工作旨在研究甲苯磺丁脲对细胞色素P450介导的非那西丁代谢的影响，反之亦然。
在本研究中，比较了单独给药或同时给药时非那西丁和甲苯磺丁脲（分别为大鼠CYP1A2和CYP2C6/11代谢活性的标志物）的生物转化速率。使用了离体灌注大鼠肝脏模型。
非那西丁对甲苯磺丁脲的羟基化无显著影响。向灌注介质中添加甲苯磺丁脲显著提高了非那西丁的O-去乙基化速率。
将两种模型底物联合使用与常规方法（单一标志物给药）进行评估时，可观察到细胞色素P450介导的代谢速率存在一些差异。由于这些差异，上述方法获得的结果可能无法完全可比。
