Multiple intragastric treatment versus continuous administration via the diet. Comparative pharmacokinetics of...

1. Abecarnil was administered to female mice at doses of 5, 50 and 150 mg/kg per day for 4 weeks either intragastrically once a day or was offered continuously via the diet. 2. On days 1, 7, 14 and 28 plasma level profiles (0-24 h) were determined in identical groups of animals. Additionally, faecal excretion of abecarnil and distribution in brain, liver and kidney was measured. 3. Drug administration via the diet was characterized by: (a) a circadian rhythm of concentrations with highs at night and lows during the day; (b) a dose-proportional increase in AUC and mean plasma levels; (c) slight accumulation in the plasma after the two higher doses. 4. Intragastric treatment resulted in: (a) clearly distinguishable absorption and disposition phases in the plasma with prominent peaks; (b) slight accumulation at the two higher doses; (c) dose-proportionality for the 50 and 150 mg/kg doses. 5. Drug load after the two routes of administration was different resulting in four times higher peak plasma levels and in double AUC values after intragastric administration than after the diet.