Objective: To investigate whether pregnane X receptor (PXR) is involved in the induction of rat hepatic cytochrome P450 3A1/2 by zolmitriptan.
Methods: The induction effects of zolmitriptan were investigated in three concentrations (100 micromol L(-1)), 50 micromolL(-1)) and 10 micromol L(-1))) using luciferase report gene method based on PXR. Pregnenolone-16 alpha-carbonitrile (PCN) was used as the positive control and the solvent DMSO as the negative control.
Result: Compared with the negative groups, the positive and high level zolmitriptan groups exhibited a significant induction effect on CYP 3A1, the activity increased to 1.93 and 1.96 times, respectively (P<0.05). The positive, middle level and low level zolmitriptan groups exhibited a significant induction effect on CYP 3A2, the activity increase to 2.51, 2.10 and 1.63 times, respectively (P<0.01, <0.05 ).
Conclusion: Zolmitriptan can significantly induce CYP 3A2 in low and middle concentrations and induce CYP 3A1 in high concentration.PXR is involved in the induction of CYP 3A1/2 by zolmitriptan.