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Aim:To determine the pharmacokinetics associated with acute toxic doses ofCPU0213,a novel endothelin receptor antagonist in mice after a single intrave-nous administration.Methods:Concentrations in serum and the pharmacokineticparameters 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 alsoassessed in mice.Results:A simple,sensitive and selective HPLC method wasdeveloped for quantitative determination of CPU0213 in mouse serum.The con-centration-time data conform to a 2-compartment model after iv administration ofCPU0213 at concentrations of 25,50,100 mg/kg.The corresponding distributionhalf-lives(T_(1/2α)) were 3.6,4.2,1.1 min and the elimination half-lives(T_(1/2β))were39.4,70.3,61.9 rain.There was a linear increase in C_0 proportional to dose,and thesame as AUC_(0-t) and AUC_(0-∞).AUC_(0-t) and AUC_(0-∞) 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 LD_(50) was 315.5mg/kg.Conclusion:First order rate pharmacokinetics were observed for CPU0213within the range of doses used,and the acute toxicity of CPU0213 is mild.
Aim: To determine the pharmacokinetics associated with acute toxic doses of CPU0213, a novel endothelin receptor antagonist in mice after a single intrave nous 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. 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 con-centration-time data conform to a 2-compartment model after iv administration of CPU0213 at concentrations of 25, 50, 100 mg / kg.The corresponding distributionhalf-lives (T_ (1/2)) were 3.6, 4.2, 1.1 min and the elimination half-lives (T_ (1 / 2β)) were39.4, 70.3, 61.9 rain. Here was a linear increase in C_0 proportional to dose, and thesame as AUC_ (0-t) and AUC_ (0 -∞). AUC_ (0-t) and AUC_ (0-∞) 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 LD_ (50) was 315.5 mg / kg.Conclusion: First order rate pharmacokinetics were observed for CPU0213within the range of doses used, and the acute toxicity of CPU0213 is mild.