Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, China.
Drugs R D. 2010;10(2):83-90. doi: 10.2165/11539320-000000000-00000.
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.
To investigate the metabolism, disposition, and metabolites of tribendimidine in healthy human volunteers.
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.
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.
These results reveal the disposition, metabolism, and main metabolites of tribendimidine in healthy Chinese volunteers.
替苯咪唑是中国科学家合成的一种新型驱虫药。它是一种广谱驱虫药,对寄生虫具有高活性。然而,其处置和代谢仍不清楚。
研究替苯咪唑在健康志愿者体内的代谢、处置和代谢物。
经过临床健康评估和实验室检查,选择 12 名健康的中国志愿者,给予替苯咪唑 400mg 肠溶片单剂量口服。在预定时间点采集血样和尿样。分别采用液相色谱-质谱(LC-MS)和高效液相色谱(HPLC)法对样品进行定性和定量分析。
替苯咪唑迅速且完全分解为 p-(1-二甲基氨基乙基亚氨基)苯胺(dADT)和对苯二甲醛(TPAL)。此外,dADT 部分转化为乙酰化 dADT,TPAL 完全转化为对苯二甲酸(TPAC)。dADT 的主要药代动力学参数(±SD)如下:消除半衰期(t(½))4.74±1.80 h;消除速率常数(K(e))0.16±0.06 h(-1);表观分布容积(Vd/F)12.23±8.69 Lkg(-1);药物从血浆中的表观总清除率(CL/F)1.63±0.58 Lh(-1)kg(-1);0 至 24 小时的血浆浓度-时间曲线下面积(AUC)(24)4.29±1.88μgmL(-1)h;从零时到无穷大的 AUC(AUC(infinity))4.45±1.81μgmL(-1)h;最大血浆药物浓度(C(max))0.64±0.27μgmL(-1);和 C(max)的时间(t(max))4.20±0.71 h。替苯咪唑给药后 24 小时内,35.28%的 dADT 和 28.50%的 TPAC 通过尿液排出。
这些结果揭示了替苯咪唑在健康中国志愿者体内的处置、代谢和主要代谢物。