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 400 mg 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 (t(½)) 4.74 ± 1.80 h; elimination rate constant (K(e)) 0.16 ± 0.06 h-1; apparent volume of distribution (Vd/F) 12.23 ± 8.69 L * kg(-1); apparent total clearance of the drug from plasma (CL/F) 1.63 ± 0.58 L * h(-1) * kg(-1); area under the plasma concentration-time curve (AUC) from time 0 to time 24 hours (AUC(24)) 4.29 ± 1.88 μg * mL(-1) * h; AUC from time zero to infinity (AUC(infinity)) 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.


CONCLUSIONS
These results reveal the disposition, metabolism, and main metabolites of tribendimidine in healthy Chinese volunteers.
Yuan
Guiyan
G
Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, China.
Xu
Jie
J
Qu
Tingting
T
Wang
Benjie
B
Zhang
Rui
R
Wei
Chunmin
C
Guo
Ruichen
R
D000328:Adult; D000871:Anthelmintics / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002681:China; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D010655:Phenylenediamines / Q000378:metabolism / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D055815:Young Adult
D000871:Anthelmintics; D010655:Phenylenediamines; C056017:tribendimidine