Yi-ming LIU , Ying-chun LIU , Huan-zhong DING , Bing-hu FANG , Fan YANG , Qi SHAN , Zhen-ling ZENG
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引用次数: 11
Abstract
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 3×3 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 (Cmax) of M1 and M2 after intravenous administration of MEQ were (5.27±1.59) μg mL−1 at 1.78 h and (1.01±0.29) μg mL−1 at 0.92 h, respectively. The mean maximum concentrations (Cmax) of MEQ, M1, and M2 were found to be (6.96±3.23), (6.61±1.56), and (0.78 ±0.25) μg 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) μg mL−1, respectively at 0.40, 1.57, and 2.00 h, respectively after oral administration of MEQ. The apparent elimination half-lives (t1/2) 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 (AUC0- of MEQ, M1, and M2 were (4.88±1.54), (36.93±17.50), and (5.16±1.94) μg h mL-1, respectively after intravenous administration of MEQ; (4.18±0.76), (48.25±20.82), and (4.88±2.21) μg h mL−1, respectively after intramuscular administration of MEQ; and (1.01±0.40), (48.83±20.71), and (5.54±2.23) μg 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.
摘要本文研究了新合成的喹诺啉1,4-二氧化衍生物甲喹诺酮(MEQ)及其两种主要代谢物M1[2-异乙醇甲喹诺酮]、M2[2-异乙醇1-脱氧甲喹诺酮]在健康猪体内的药动学。在随机3×3交叉设计中，9头健康交叉面包猪通过口服、肌肉注射和静脉注射MEQ (10 mg kg - 1体重)，洗脱期为1周。采用高效液相色谱(HPLC)法测定MEQ及其代谢产物M1、M2的血药浓度。采用WinNonlin 5.2软件对MEQ及其代谢物M1和M2的血药浓度随时间变化曲线进行非区隔分析。静脉给药MEQ后，M1和M2的平均最大浓度(Cmax)分别为(5.27±1.59)μ mL−1和(1.01±0.29)μ mL−1。肌注MEQ后0.15、1.61、1.30 h MEQ、M1、M2的平均最大浓度(Cmax)分别为(6.96±3.23)、(6.61±1.56)、(0.78±0.25)μ mL - 1，口服MEQ后0.40、1.57、2.00 h MEQ的平均最大浓度分别为(0.75±0.45)、(6.90±1.52)、(0.62±0.21)μ mL - 1。静脉给药MEQ后，MEQ、M1、M2的表观消除半衰期(t1/2)分别为(0.84±0.35)、(7.57±3.93)、(9.56±6.00)h;肌注MEQ后分别为(0.50±0.25)、(6.30±3.00)、(5.94±2.54)h;口服MEQ后分别为(1.64±1.17)、(5.59±1.93)、(16.25±10.27)h。静脉给药MEQ后，MEQ、M1、M2的血药浓度-时间曲线下平均面积AUC0-分别为(4.88±1.54)、(36.93±17.50)、(5.16±1.94)μg h mL-1;肌注MEQ后分别为(4.18±0.76)、(48.25±20.82)、(4.88±2.21)μg h mL−1;分别为(1.01±0.40)、(48.83±20.71)、(5.54±2.23)μg h mL−1。经口服、肌肉和静脉给药后，MEQ在猪体内被迅速吸收和代谢。口服MEQ后血药浓度-时间曲线的双峰现象及其他代谢物的药代动力学有待进一步研究。
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