Pharmacokinetics of Mequindox and Its Metabolites in Swine  

作　　者：LIU Yi-ming LIU Ying-chun DING Huan-zhong FANG Bing-hu YANG Fan SHAN Qi ZENGZhen-ling 

机构地区：[1]Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510640, P.R.China [2]Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200232, P.R.China

出　　处：《Agricultural Sciences in China》2011年第12期1968-1976,共9页中国农业科学（英文版）

基　　金：supported by the National Basic Research Program of China (973 Program,2009CB118805);the National Key Technology Research and Development Program of China during the 10th Five-Year Plan Period (2009BADB7B05-03)

摘　　要：The present study was carried out to investigate the pharmacokinetics of mequindox （MEQ）, a new synthetic quinoxaline 1,4-dioxide derivative and its two main metabolites M1 [2-isoethanol mequinoox], M2 [2-isoethanol 1-desoxymequindox] in healthy swine. MEQ （10 mg kg-1 body weight） was administered to nine healthy cross-bread swine via oral, intramuscular, and intravenous routes in a randomized 3x3 crossover design with a 1-wk washout period. A sensitive high-performance liquid chromatography （HPLC） method was used for the determination of plasma concentrations of MEQ and its metabolites M1 and M2. Plasma concentration versus time profiles of MEQ and its metabolites, M1 and M2, were analyzed by noncompartmental analysis using WinNonlin 5.2 software. The mean maximum concentrations （Cmax） of M1 and M2 after intravenous administration of MEQ were （5.27±1.59） lag mL-1 at 1.78 h and （1.01±0.29） μg mL-1 at 0.92 h, respectively. The mean maximum concentrations （Cmax） ofMEQ, M1, and M2 were found to be （6.96±3.23）, （6.61±1.56）, and （0.78 ±0.25） lag mL-1 respectively at 0.15, 1.61, and 1.30 h after intramuscular administration of MEQ, respectively and （0.75±0.45）, （6.90±1.52）, and （0.62±0.21） lag mL-1, respectively at 0.40, 1.57, and 2.00 h, respectively after oral administration of MEQ. The apparent elimination half-lives （b2） ofMEQ, M1, and M2 were （0.84±0.35）, （7.57±3.93）, and （9.56±6.00） h, respectively after intravenous administration of MEQ; （0.50±0.25）, （6.30±3.00）, and （5.94±2.54） h, respectively after intramuscular administration of MEQ; and （1.64± 1.17）, （5.59±1.93）, and （16.25±10.27） h, respectively after oral administration of MEQ. The mean areas under the plasma concentration-time curve （AUC0-∝） of MEQ, M1, and M2 were （4.88±1.54）, （36.93±17.50）, and （5.16±94） μg h mL-1, respectively after intravenous administration of MEQ; （4.18±0.76）, （48.25±20.82）, and （4.88±2.21�The present study was carried out to investigate the pharmacokinetics of mequindox （MEQ）, a new synthetic quinoxaline 1,4-dioxide derivative and its two main metabolites M1 [2-isoethanol mequinoox], M2 [2-isoethanol 1-desoxymequindox] in healthy swine. MEQ （10 mg kg-1 body weight） was administered to nine healthy cross-bread swine via oral, intramuscular, and intravenous routes in a randomized 3x3 crossover design with a 1-wk washout period. A sensitive high-performance liquid chromatography （HPLC） method was used for the determination of plasma concentrations of MEQ and its metabolites M1 and M2. Plasma concentration versus time profiles of MEQ and its metabolites, M1 and M2, were analyzed by noncompartmental analysis using WinNonlin 5.2 software. The mean maximum concentrations （Cmax） of M1 and M2 after intravenous administration of MEQ were （5.27±1.59） lag mL-1 at 1.78 h and （1.01±0.29） μg mL-1 at 0.92 h, respectively. The mean maximum concentrations （Cmax） ofMEQ, M1, and M2 were found to be （6.96±3.23）, （6.61±1.56）, and （0.78 ±0.25） lag mL-1 respectively at 0.15, 1.61, and 1.30 h after intramuscular administration of MEQ, respectively and （0.75±0.45）, （6.90±1.52）, and （0.62±0.21） lag mL-1, respectively at 0.40, 1.57, and 2.00 h, respectively after oral administration of MEQ. The apparent elimination half-lives （b2） ofMEQ, M1, and M2 were （0.84±0.35）, （7.57±3.93）, and （9.56±6.00） h, respectively after intravenous administration of MEQ; （0.50±0.25）, （6.30±3.00）, and （5.94±2.54） h, respectively after intramuscular administration of MEQ; and （1.64± 1.17）, （5.59±1.93）, and （16.25±10.27） h, respectively after oral administration of MEQ. The mean areas under the plasma concentration-time curve （AUC0-∝） of MEQ, M1, and M2 were （4.88±1.54）, （36.93±17.50）, and （5.16±94） μg h mL-1, respectively after intravenous administration of MEQ; （4.18±0.76）, （48.25±20.82）, and （4.88±2.21�

关 键 词：MEQUINDOX METABOLITES PHARMACOKINETICS HPLC SWINE 

分 类 号：S859.796[农业科学—临床兽医学] S858.28[农业科学—兽医学]