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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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Chromatograms of (a) blank urine and (b) urine collected 4 hours after administration of tribendimidine. Peaks 1 and 2 in (b) correspond to the peak retention times of acylated p-(1-dimethylamino ethylimino) aniline (dADT) and dADT, respectively (see figure 4 for more detailed analysis).
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Fig3: Chromatograms of (a) blank urine and (b) urine collected 4 hours after administration of tribendimidine. Peaks 1 and 2 in (b) correspond to the peak retention times of acylated p-(1-dimethylamino ethylimino) aniline (dADT) and dADT, respectively (see figure 4 for more detailed analysis).

Mentions: The chromatograms of blank urine samples and urine samples collected after oral administration of tribendimidine are shown in figure 3. Two peaks of retention time, 3.2 minutes and 4.1 minutes, were validated by LC-MS. Peak 1 (protonated molecular ion [M + H]+, 220.2) and peak 2 ([M + H]+, 178.2) are shown in figures 4a and 4b, respectively. Peak 2 is dADT and peak 1 is the acetylated metabolite of dADT based on their molecular weight and standard.


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)

Chromatograms of (a) blank urine and (b) urine collected 4 hours after administration of tribendimidine. Peaks 1 and 2 in (b) correspond to the peak retention times of acylated p-(1-dimethylamino ethylimino) aniline (dADT) and dADT, respectively (see figure 4 for more detailed analysis).
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Related In: Results  -  Collection

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

Fig3: Chromatograms of (a) blank urine and (b) urine collected 4 hours after administration of tribendimidine. Peaks 1 and 2 in (b) correspond to the peak retention times of acylated p-(1-dimethylamino ethylimino) aniline (dADT) and dADT, respectively (see figure 4 for more detailed analysis).
Mentions: The chromatograms of blank urine samples and urine samples collected after oral administration of tribendimidine are shown in figure 3. Two peaks of retention time, 3.2 minutes and 4.1 minutes, were validated by LC-MS. Peak 1 (protonated molecular ion [M + H]+, 220.2) and peak 2 ([M + H]+, 178.2) are shown in figures 4a and 4b, respectively. Peak 2 is dADT and peak 1 is the acetylated metabolite of dADT based on their molecular weight and standard.

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