[Induction of rat hepatic cytochrome P-450 3A by zolmitriptan mediated with pregnane X receptor].
To investigate whether pregnane X receptor (PXR) is involved in the induction of rat hepatic cytochrome P450 3A1/2 by zolmitriptan.



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.



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 ).



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.
Xing
Feng
F
Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Yu
Lu-Shan
LS
Zeng
Su
S
D000818:Animals; D051544:Cytochrome P-450 CYP3A / Q000187:drug effects* / Q000378:metabolism*; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D023303:Oxazolidinones / Q000494:pharmacology*; D000077297:Pregnane X Receptor; D051381:Rats; D011987:Receptors, Steroid / Q000378:metabolism / Q000502:physiology*; D014363:Tryptamines / Q000494:pharmacology*
D023303:Oxazolidinones; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D014363:Tryptamines; C089750:zolmitriptan; D051544:Cytochrome P-450 CYP3A