The effect of food on the bioavailability and kinetics of the anticancer drug amsacrine and a new analogue, N-5-dimethyl-9-[(2-methoxy-4-methylsulphonylamino)phenylamino]-4 acridinecarboxamide in rabbits.

Abstract

Both amsacrine and its analogue, N-5-dimethyl-9-[(2-methoxy-4- methylsulphonylamino)phenylamino]-4-acridinecarboxamide (CI-921) are absorbed from the gastrointestinal tract in rabbits. The mean bioavailability for amsacrine was 50% +/- 17 (s.d.) in non-fasting animals, and was significantly increased in fasting animals (mean, 90% +/- 10). The bioavailability for CI-921 (mean, 26% +/- 11) in the non-fasting animal was significantly less than that found for amsacrine, but this difference disappeared in the fasting animal when the bioavailability of CI-921 was significantly increased to 69% +/- 23. Oral administration of both agents resulted in significantly prolonged elimination half-lives and mean residence times compared to the i.v. infusion, but no significant difference was observed in these parameters between the fasting and non-fasting state. This study suggests that oral dosing may be a possible alternative route for the administration of these anticancer agents.