Effects of vindoline on rat cytochrome P450 isoform activities in vitro

Abstract

A specific ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) method has been described for the simultaneous determination of the metabolites of tacrine, bupropion, diclofenac, dextromethorphan and midazolam, which are the five probe drugs of the five cytochrome P450 (CYP450) isoforms CYP1A2, CYP2B, CYP2C11, CYP2D1 and CYP3A4.The inhibition degree was determined by calculating the IC 50 . The chromatographic separation was performed on a C 18 column with a mobile phase consisting of 0.1% formic acid and acetonitrile. The mass spectrometric analysis was conducted in positive electrospray ionization mode. The IC 50 values of CYP1A2, CYP2B, CYP2C11, CYP2D1 and CYP3A were 113.4, 83.78, 22.50, 9.081 and 52.76 μmol L À1 , respectively. The in vitro results demonstrated that vindoline could inhibit CYP2D1 activity in rats, and weak inhibitory effect on CYP2C11 and CYP3A, but had no obvious effects on CYP1A2 and CYP2B.

Evaluation of the impact of vindoline, an active components of Catharanthus roseus, on rat hepatic cytochrome P450 enzymes by using a cocktail of probe drugs

“…In the previous in vitro experiments, it was found that VDL could inhibit CYP2D1 activity, and had weak inhibitory effect on CYP2C11 and CYP3A ( S1 Fig ), which was inconsistent with the results of in vivo experiments [ 44 ]. The reasons for this phenomenon may be as follows: (1) Influence of in vivo and in vitro action time and dosage: in vitro experiments, VDL and probe drugs were directly incubated with CYP450 enzymes in rat liver microsome, while in vivo experiments, rats were pretreated with VDL for 15 days, and then the probe substrate was administered on the 16 days.…”