The objective of this work was to investigate the effect of orally administered silybin on the pharmacokinetics of imatinib in rats and the metabolism of imatinib in human liver microsome and rat liver microsomes. Eighteen healthy male SD rats were randomly divided into 3 groups: group A (control group), group B (received multiple doses of 50 mg·kg(-1) silybin for 15 consecutive days), and group C (received a single dose of 50 mg·kg(-1) silybin). A single dose of imatinib was administered orally 30 min after administration of silybin (50 mg·kg(-1)). Imatinib plasma levels were measured by UPLC-MS/MS, and pharmacokinetic parameters were calculated by DAS 3.0 software (Bontz Inc., Beijing, China). In addition, human and rat liver microsome were performed to determine the effects of silybin metabolism of imatinib in vitro. The multiple doses or single dose of 50 mg·kg(-1) silybin significantly decreased the area under the curve (0-t) of imatinib (p < 0.01). And the half-life (t1/2) of imatinib is significantly increased (p < 0.05 and p < 0.01, respectively). Also, silybin showed inhibitory effect on human and rat microsomes, the IC50 of silybin were 26.42 μmol·L(-1) and 49.12 μmol·L(-1) in human and rat liver microsomes, respectively. These results indicate that more attention should be paid to when imatinib is administrated combined with silybin.
Keywords: UPLC-MS/MS; cytochromes P450; drug interaction; imatinib mesylate; interaction médicamenteuse; microsomes; mésilate d’imatinib.