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 (T½α) were 3.6, 4.2, 1.1 min and the elimination half-lives (T½β) 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.
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Project supported by a key project from the National Natural Science Foundation of China (No 30230170).
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Guan, L., Feng, Y., Ji, M. et al. Pharmacokinetics of CPU0213, a novel endothelin receptor antagonist, after intravenous administration in mice. Acta Pharmacol Sin 27, 367–371 (2006). https://doi.org/10.1111/j.1745-7254.2006.00288.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00288.x