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Metabolism and disposition of tribendimidine and its metabolites in healthy Chinese volunteers.

Yuan G, Xu J, Qu T, Wang B, Zhang R, Wei C, Guo R - Drugs R D (2010)

Bottom Line: Tribendimidine was rapidly and completely broken down to p-(1-dimethylamino ethylimino) aniline (dADT) and terephthalaldehyde (TPAL).A total of 35.28% dADT and 28.50% TPAC were excreted through the urine within 24 hours after tribendimidine administration.These results reveal the disposition, metabolism, and main metabolites of tribendimidine in healthy Chinese volunteers.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, China.

ABSTRACT

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.

Conclusion: These results reveal the disposition, metabolism, and main metabolites of tribendimidine in healthy Chinese volunteers.

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The breakdown of tribendimidine in the human body. dADT = p-(1-dimethylamino ethylimino) aniline; TPAC = terephalic acid; TPAL = terephthalaldehyde.
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Fig5: The breakdown of tribendimidine in the human body. dADT = p-(1-dimethylamino ethylimino) aniline; TPAC = terephalic acid; TPAL = terephthalaldehyde.

Mentions: The results indicated that tribendimidine was immediately broken down to dADT and TPAL after oral administration of enteric-coated tablets. dADT in plasma can be used to evaluate the pharmacokinetic behavior of tribendimidine in vivo after its oral administration. The metabolite TPAL was also not detected in either urine or plasma, because it was quickly metabolized to a more stable metabolite (TPAC), which was found in urine. dADT was further metabolized to an acetylated form by acetyltransferase, as shown in figure 5.


Metabolism and disposition of tribendimidine and its metabolites in healthy Chinese volunteers.

Yuan G, Xu J, Qu T, Wang B, Zhang R, Wei C, Guo R - Drugs R D (2010)

The breakdown of tribendimidine in the human body. dADT = p-(1-dimethylamino ethylimino) aniline; TPAC = terephalic acid; TPAL = terephthalaldehyde.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585841&req=5

Fig5: The breakdown of tribendimidine in the human body. dADT = p-(1-dimethylamino ethylimino) aniline; TPAC = terephalic acid; TPAL = terephthalaldehyde.
Mentions: The results indicated that tribendimidine was immediately broken down to dADT and TPAL after oral administration of enteric-coated tablets. dADT in plasma can be used to evaluate the pharmacokinetic behavior of tribendimidine in vivo after its oral administration. The metabolite TPAL was also not detected in either urine or plasma, because it was quickly metabolized to a more stable metabolite (TPAC), which was found in urine. dADT was further metabolized to an acetylated form by acetyltransferase, as shown in figure 5.

Bottom Line: Tribendimidine was rapidly and completely broken down to p-(1-dimethylamino ethylimino) aniline (dADT) and terephthalaldehyde (TPAL).A total of 35.28% dADT and 28.50% TPAC were excreted through the urine within 24 hours after tribendimidine administration.These results reveal the disposition, metabolism, and main metabolites of tribendimidine in healthy Chinese volunteers.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, China.

ABSTRACT

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.

Conclusion: These results reveal the disposition, metabolism, and main metabolites of tribendimidine in healthy Chinese volunteers.

Show MeSH
Related in: MedlinePlus