Multiple intragastric treatment versus continuous administration via the diet. Comparative pharmacokinetics of abecarnil in mouse.
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.
Research Laboratories of Schering AG, Free University of Berlin, Institute of Pharmacy.
W
W
Krause
F
F
Reissmann
C
C
Schöbel
W
W
Schunack
D000284:Administration, Oral; D000818:Animals; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism; D002243:Carbolines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008954:Models, Biological; D015233:Models, Statistical; D014018:Tissue Distribution
D014151:Anti-Anxiety Agents; D002243:Carbolines; C062769:abecarnil