Abstract:

Objective To study the pharmacokinetics of tribendimidine in rat plasma and bile. Methods Twenty male Sprague Dawley rats were randomly assigned into control and tribendimidine groups (n = 10 in each). Rats in the tribendimidine group were further divided into two batches after oral gavage of 200 mg/kg tribendimidine: 5 were used for orbital blood collection at 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 24.0 and 36.0 h after administration, while the other 5 were used for bile collection at 0.5-1.0, 1.0-1.5, 1.5-2.0, 2.0-2.5, 2.5-3.0, 3.0-3.5, 3.5-4.0, 4.0-4.5, 4.5-5.0, 5.0-5.5, 5.5-6.0, 6.0-6.5, 6.5-7.5, 7.5-8.5, 8.5-9.5, and 9.5-10.5 h. Rats in the control group received same operations except that no tribendimidine was administered. After optimizing HPLC detection conditions, concentrations of p-（1-dimethylamino ethylimino） aniline （dADT） in rat plasma and bile were measured. The concentrations were plotted against time, and curves for bile excretion rate and cumulative excretion were drawn. Results The time for maximum dADT （T_max） and the maximum concentration of dADT （C_max） in plasma were （0.9 ± 0.2） h and （8.1 ± 2.1） mg/L, respectively, and those in the bile were （1.2 ± 0.4） h and （11.2 ± 2.1） mg/L, respectively. The bile excretion rate was highest during 0.5-3.0 h after administration, and the cumulative excretion quantity of dADT was（40.1 ± 12.0） μg within 11 h, with a cumulative excretion rate of 0.57‰. Conclusion The tribendimidine metabolite dADT shows a higher concentration and a longer stay in the bile than in the plasma, which may be beneficial for the treatment of Clonorchis sinensis that parasitizes in the biliary tract.

Key words: Tribendimidine, P-（1-dimethylamino ethylimino）aniline, Pharmacokinetics, Plasma, Bile, Clonorchis sinensis