Pharmacokinetics of CGP 6140 (amocarzine) after oral administration of single 100‐1600 mg doses to patients with onchocerciasis

The concentrations of CGP 6140 [4‐nitro‐4′‐(N‐methyl‐ piperazinylthiocarbonylamido)‐diphenylamine] and of its N‐oxide metabolite, CGP 13,231, were measured in plasma and urine after single oral dose of 100‐1600 mg of CGP 6140 to 41 fasted Ghanaian patients with Onchocerca volvulus infections. The absorption of CGP 6140 was rapid and its terminal elimination half‐life was about 3 h. The plasma concentrations of CGP 6140 were essentially proportional to the dose. A greater variability in plasma concentrations was apparent after the 800 and 1600 mg doses indicating a poor bioavailability of the drug administered in fasting conditions to several patients. In plasma, the concentrations of CGP 13,231 were similar to those of CGP 6140. The amount of CGP 13,231 excreted in urine was 25‐40% of the dose of CGP 6140 whereas only 1.5% was excreted as unchanged drug. If a single dose of drug is used for the treatment, the plasma concentration would be maintained for 3‐4 h at a high level. At 8 h, the concentration falls to about 10% of the Cmax. If sustained plasma concentrations of the drug are needed for efficacy, twice daily administration would maintain the minimum concentration at about 10% of the Cmax.