Metabolism and Disposition of Tribendimidine and Its Metabolites in Healthy Chinese Volunteers.

Background: Tribendimidine is a new anthelmintic agent synthesized by Chinese scientists. It is a broad spectrum agent with high activity against parasites. However, its disposition and metabolism remain unknown. Objective: To investigate the metabolism, disposition, and metabolites of tribendimidine in healthy human volunteers. Methods: Twelve healthy Chinese volunteers were chosen after clinical assessment of health status and laboratory tests. They received single oral doses of tribendimidine 400mg enteric-coated tablets. Blood and urine samples were collected at scheduled timepoints. Samples were qualitatively and quantitatively analyzed by liquid chromatography-mass spectrometric (LC-MS) and high performance liquid chromatography (HPLC) methods, respectively. Results: Tribendimidine was rapidly and completely broken down to p-(1-dimethylamino ethylimino) aniline (dADT) and terephthalaldehyde (TPAL). Furthermore, dADT was partially transformed to acetylated dADT, and TPAL completely transformed to terephalic acid (TPAC). The main pharmacokinetic parameters (± SD) of dADT were as follows: elimination half life (t½) 4.74 ± 1.80 h; elimination rate constant (K_e) 0.16 ± 0.06 h^-1; apparent volume of distribution (Vd/F) 12.23 ± 8.69L · kg^-1; apparent total clearance of the drug from plasma (CL/F) 1.63 ± 0.58L · h-1 kg-1; area under the plasma concentration-time curve (AUC) from time 0 to time 24 hours (AUC₂₄) 4.29 ± 1.88 µg · mL^-1 · h; AUC from time zero to infinity (AUC∞) 4.45 ± 1.81 µg · mL^-1 h; maximum plasma drug concentration (C_max) 0.64 ± 0.27 µg · mL^-1; and time to C_max (t_max) 4.20 ± 0.71 h. A total of 35.28% dADT and 28.50% TPAC were excreted through the urine within 24 hours after tribendimidine administration. Conclusion: These results reveal the disposition, metabolism, and main metabolites of tribendimidine in healthy Chinese volunteers. [ABSTRACT FROM AUTHOR]