Pharmacokinetics of Mequindox and Its Metabolites in Swine

文献类型： 外文期刊

第一作者： Liu Yi-ming

作者： Liu Yi-ming;Liu Ying-chun;Ding Huan-zhong;Fang Bing-hu;Yang Fan;Shan Qi;Zeng Zhen-ling;Liu Ying-chun

作者机构：

关键词： mequindox;metabolites;pharmacokinetics;HPLC;swine

期刊名称：AGRICULTURAL SCIENCES IN CHINA （ 影响因子：0.82； 五年影响因子：0.997 ）

ISSN： 1671-2927

年卷期： 2011 年 10 卷 12 期

页码：

收录情况： SCI

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 non-compartmental analysis using WinNonlin 5.2 software. The mean maximum concentrations (C(max)) of M1 and M2 after intravenous administration of MEQ were (5.27 +/- 1.59) mu g mL(-1) at 1.78 h and (1.01 +/- 0.29) mu g mL(-1) at 0.92 h, respectively. The mean maximum concentrations (C(max)) of MEQ, M1, and M2 were found to be (6.96 +/- 3.23), (6.61 +/- 1.56), and (0.78 +/- 0.25) mu g 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) mu g mL(-1), respectively at 0.40, 1.57, and 2.00 h, respectively after oral administration of MEQ. The apparent elimination half-lives (t(1/2)) of MEQ, 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 (AUC(0-infinity)) of MEQ, M1, and M2 were (4.88 +/- 1.54), (36.93 +/- 17.50), and (5.16 +/- 1.94) mu g h mL(-1), respectively after intravenous administration of MEQ; (4.18 +/- 0.76), (48.25 +/- 20.82), and (4.88 +/- 2.21) mu g h mL(-1), respectively after intramuscular administration of MEQ; and (1.01 +/- 0.40), (48.83 +/- 20.71), and (5.54 +/- 2.23) mu g h mL(-1), respectively after oral administration of MEQ. MEQ was rapidly absorbed and metabolized in swine after oral, intramuscular, and intravenous administration. Further studies are required to investigate the double-peak phenomenon observed in the plasma concentration-time profile after oral administration and the pharmacokinetics of other metabolites of MEQ.

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