암브록솔과 세티리진의 Cytochrome P450 저해 활성 평가

In Vitro Assessment of Cytochrome P450 Inhibition by Ambroxol and Cetirizine

In the present study we evaluated drug-drug interaction potential of ambroxol and cetirizine mediated by inhi-bition of CYP isoforms including CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 using pooled human liver microsomes (HLMs). As measured by liquid chromatography-electrospray ionization tandem mass pec- trometry, cetirizine and ambroxol inhibited significantly CYP2E1 but the maximal inhibition was approximately 36% at 10 µM cetirizine and 28% at 3 µM ambroxol. In addition, CYP2D6 activity was decreased to approximately 83% of ontrol activity in pooled HLM incubated with 3 µM ambroxol. Activities of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, and CYP3A4 were not significantly inhibited by cetirizine and ambroxol. Considering their maximal plasma concentration in human (Cmax of cetirizine is approximately 0.67 µM and Cmax of ambroxol is 0.044 µM), these two drugs have very low pos- sibility in drug-drug interaction by CYP inhibition in clinical situations.