The Effect of Apigenin on Pharmacokinetics of Imatinib and Its Metabolite N-Desmethyl Imatinib in Rats

The purpose of this study was to determine the effect of apigenin on the pharmacokinetics of imatinib and N-desmethyl imatinib in rats. Healthy male SD rats were randomly divided into four groups: A group (the control group), B group (the long-term administration of 165 mg/kg apigenin for 15 days), C group (a single dose of 165 mg/kg apigenin), and D group (a single dose of 252 mg/kg apigenin). The serum concentrations of imatinib and N-desmethyl imatinib were measured by HPLC, and pharmacokinetic parameters were calculated using DAS 3.0 software. The parameters of AUC((0-t)), AUC((0-infinity)), T-max, V-z/F and CLz/F for imatinib in group B were different from those in group A (P < 0.05). Besides, MRT(0-t) and MRT(0-infinity) in groups C and D differed distinctly from those in group A as well. The parameters of AUC((0-t)) and C-max for N-desmethyl imatinib in group C were significantly lower than those in group A (P < 0.05); however, compared with groups B and D, the magnitude of effect was modest. Those results indicated that apigenin in the short-term study inhibited the metabolism of imatinib and its metabolite N-desmethyl imatinib, while in the long-term study the metabolism could be accelerated.