@article{APS3834,
author = {Li Guan and Yu Feng and Min Ji and De-zai Dai},
title = {Pharmacokinetics of CPU0213, a novel endothelin receptor antagonist, after intravenous administration in mice},
journal = {Acta Pharmacologica Sinica},
volume = {27},
number = {3},
year = {2016},
keywords = {},
abstract = {Aim: To determine the pharmacokinetics associated with acute toxic doses of CPU0213, a novel endothelin receptor antagonist in mice after a single intravenous administration.
Methods: Concentrations in serum and the pharmacokinetic parameters of CPU0213 were assayed by high pressure liquid chromatography (HPLC) following a single intravenous bolus of CPU0213 at concentrations of 25, 50, and 100 mg/kg in mice. The intravenous acute toxicity of CPU0213 was also assessed in mice.
Results: A simple, sensitive and selective HPLC method was developed for quantitative determination of CPU0213 in mouse serum. The concentration-time data conform to a 2-compartment model after iv administration of CPU0213 at concentrations of 25, 50, 100 mg/kg. The corresponding distribution half-lives (T1/2α) were 3.6, 4.2, 1.1 min and the elimination half-lives (T1/2β) were 39.4, 70.3, 61.9 min. There was a linear increase in C0 proportional to dose, and the same as AUC0–t and AUC0–∞. AUC0–t and AUC0–∞ were 4.511, 13.070, 23.666 g·min·L-1 and 4.596, 13.679, 24.115 g·min·L-1, respectively. The intravenous LD50 was 315.5 mg/kg.
Conclusion: First order rate pharmacokinetics were observed for CPU0213 within the range of doses used, and the acute toxicity of CPU0213 is mild.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/3834}
}