Open AccessPharmacokinetics of CPU0213, a novel endothelin receptor antagonist, after intravenous administration in mice 1
Author(s) -
GUAN Li,
FENG Yu,
JI Min,
DAI Dezai
Publication year - 2006
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2006.00288.x
Subject(s) - pharmacokinetics , high performance liquid chromatography , pharmacology , bolus (digestion) , intravenous bolus , chemistry , antagonist , endothelin receptor antagonist , toxicity , volume of distribution , medicine , receptor , chromatography , biochemistry
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 ( T 1/2α ) were 3.6, 4.2, 1.1 min and the elimination half‐lives ( T 1/2 α) were 39.4, 70.3, 61.9 min. There was a linear increase in C 0 proportional to dose, and the same 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 CPU0213 within the range of doses used, and the acute toxicity of CPU0213 is mild.