伊曲康唑对合用药物药代动力学的影响机制初探

目的探讨伊曲康唑对合用药物药代动力学的影响机制,为临床上安全合理地利用合成药物提供依据。方法利用健康成人的肝细胞微粒体,将其分为加入不同浓度伊曲康唑的10个小组,浓度梯度为0.0、0.4、0.8、1.6、3.2μg/ml,每组做5个平行组,之后在其中五组加入肝细胞微粒体细胞色素的P450的同功酶1A2的底物非那西丁,在另外五组中加入同工酶3A4的底物睾酮,测量不同伊曲康唑下的同功酶1A2和3A4的相对活性。结果各浓度伊曲康唑组对同功酶1A2作用效果无明显差异,各浓度伊曲康唑组对同功酶3A4的作用较明显,同功酶3A4的活性随着伊曲康唑的浓度增大而减小,其减小到本实验的最大活性一半时的伊曲康唑的浓度为0.7μg/ml。结论伊曲康唑对健康成年人肝细胞微粒体细胞色素酶同功酶1A2的活性无显著影响;但是它对同功酶3A4的活性有明显抑制作用,极大地影响了同功酶3A4对合用药物药代动力学的各种参数。

Itraconazole to Share Mechanism of the Influence of the Drug Pharmacokinetic Study

Objective To study the pharmacokinetics of itraconazole combined drugs influence mechanism of dynamics,and provide basis for clinical rational use of synthetic drugs safety. Methods Using tiver microsomes by healthy adult, divided into 10 groups with different concentrations of itraconazole, a concentration gradient is 0.0,0.4,0.8,1.6,3.2μg/ml, each doing 5 parallel groups, after the enzyme substrate 1A2 into the hepatocyte microsomal cytochrome five groups including P450 non phenacetin,joined the 3A4 isoenzyme in the five other groups in the substrate testosterone, relative activity measurements under different itraconazole isoenzymes 1A2 and 3A4. Results The concentration of the itraconazole group had no significant difference in isoenzyme 1A2 effect, effect of the concentration of the itraconazole group of isoenzyme 3A4 is obvious, 3A4 isoenzyme activity decreases with increasing the concentration of itraconazole, reduced to concentrations of itraconazole maximal activity of the half when the 0.7μg/ml. Conclusion No significant effect of active itraconazole for healthy adults of hepatocellular Microsome Cytochrome 1A2 isoenzyme; but had significant inhibition effect on 3A4 isoenzyme activity, greatly nfluences the isoenzyme 3A4 on drug pharmacokinetics parameters of dynamics.