Comparative pharmacokinetics of abecarnil in rat following single and multiple intragastric treatment and continuous administration via the diet.

The anxiolytic beta-carboline abecarnil was administered to female rats at doses of 10, 50, and 250 mg/kg/day for 4 weeks either intragastrically once a day or continuously via the feed. On days 1, 3, 7, 14, and 28, plasma level profiles (0-24 hr) and, additionally, on day 28, concentration profiles (0-24 hr) in liver, kidney, and brain were determined in identical groups of animals. Fecal excretion of unchanged abecarnil also was determined as a measure for enteric absorption. After both routes of administration, absorption was practically complete. Drug uptake via the feed resulted in a plateau-like plasma level without explicit maxima or minima. Indications were observed for a positive food intake plasma level correlation with lower plasma levels during the day and higher concentrations at night, for a slight increase of drug plasma levels during the 4-week period, and a dose-proportional increase of mean plasma concentrations. Intragastric treatment was characterized by clearly distinguishable absorption and disposition phases with prominent peaks after the 10 and 50 mg/kg doses, a plateau-like plasma level probably due to prolonged absorption after the 250 mg/kg dose, slight accumulation of drug in the plasma during continuous once-daily treatment, and a dose-proportional increase of the AUC. The drug load of the animals measured as concentrations in plasma and tissues was different after both routes of administration. Peak plasma levels were greater after intragastric treatment by a factor of 5, and the AUC was double compared to the feed experiment.(ABSTRACT TRUNCATED AT 250 WORDS)