The absorption and excretion of the peripheral vasodilator¹⁴C-mecinarone, (¹⁴C-6809 MD) in rat, dog and man

Summary

Oral doses of the peripheral vasodilator mecinarone (6809 MD), administered as the^l4C-compound, were well absorbed from the gastrointestinal tract of rats, dogs and humans. Much of the dose was excreted in 24 h 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 < dog < 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 6809 MD was probably rapidly biotransformed in rat, dog and man.