Hawkins D R, Weston K T, Chasseaud L F, Darragh A, O'Kelly A
Eur J Drug Metab Pharmacokinet. 1980;5(3):135-43. doi: 10.1007/BF03189457.
Oral doses of the peripheral vasodilator mecinarone (6809 MD), administered as the 14C-compound, were well absorbed from the gastrointestinal tract of rats, dogs and humans. Much of the dose was excreted in 24 by rats and dogs, but more slowly by humans. In 5 days, rats, dogs and humans excreted in the urine and faeces respectively means of 3.3 and 95.9%, 13.2 and 80.3%, and 22.0 and 60.8%. The proportions of radioactivity excreted in urine and faeces after intravenous doses were similar to those after oral doses, means of 3.1 and 85.0% respectively by rats and 16.8 and 78.3% by dogs. Radioactivity present in the faeces was probably mainly excreted in bile; rats (n = 2) excreted a mean of 52.3, 19.8 and 3.9% in bile, faeces and urine after oral doses. Plasma concentrations of radioactivity after oral doses reached a maximum at 1 h in rats (mean 126 ng equiv/ml), at 1 to 2 h in dogs (mean 784 ng equiv/ml) and at 1.5 to 2 h in humans (mean 547 ng equiv/ml. Only a small proportion of this radioactivity (10-30%) represented unchanged drug. When "normalised" for dose/bodyweight differences, those levels were in the ratio 1 : 7 : 32 (rat less than dog less than man). Areas under plasma radioactivity concentration-time curves after oral doses to rats and dogs were about 25% and 53% respectively of those after corresponding intravenous doses. Only about 20% of the radioactivity in the plasma of dogs at 2 min after an intravenous dose represented unchanged drug. These data suggest that 6890 MD was probably rapidly biotransformed in rat, dog and man.
以14C标记化合物形式口服外周血管扩张剂美西那龙（6809 MD）后，大鼠、狗和人类胃肠道对其吸收良好。大鼠和狗在24小时内排出了大部分剂量，但人类排出速度较慢。5天内，大鼠、狗和人类分别通过尿液和粪便排出的剂量均值为3.3%和95.9%、13.2%和80.3%、22.0%和60.8%。静脉给药后尿液和粪便中排出的放射性比例与口服给药后相似，大鼠分别为3.1%和85.0%，狗分别为16.8%和78.3%。粪便中的放射性可能主要通过胆汁排出；口服给药后，大鼠（n = 2）胆汁、粪便和尿液中的排出均值分别为52.3%、19.8%和3.9%。口服给药后，大鼠血浆放射性浓度在1小时达到峰值（均值126 ng当量/ml），狗在1至2小时达到峰值（均值784 ng当量/ml），人类在1.5至2小时达到峰值（均值547 ng当量/ml）。该放射性中只有一小部分（10 - 30%）代表未变化的药物。当根据剂量/体重差异进行“标准化”后，这些水平的比例为1 : 7 : 32（大鼠＜狗＜人）。大鼠和狗口服给药后血浆放射性浓度-时间曲线下面积分别约为相应静脉给药后的25%和53%。静脉给药后2分钟，狗血浆中只有约20%的放射性代表未变化的药物。这些数据表明，6890 MD在大鼠、狗和人类体内可能迅速发生生物转化。
