Absorption and bioavailability of captopril in mice and rats after administration by gavage and in the diet.

The absorption of captopril (I), a new antihypertensive agent, was studied in mice and rats at doses (50 and 1350 mg/kg) administered in the diet in chronic toxicological studies. 3H- or 35S-Labeled I was administered by gavage and in the diet to male and female animals in a two-way crossover study. Animals received daily doses of nonradiolabeled I in the diet for 25 days, except on Days 15 and 22 when radiolabeled I was administered either by gavage or in the diet. Absorption of the total radioactivity in 2-month-old mice averaged 49 and 48%, respectively, of the 50- and 1350-mg/kg doses given in the diet and 57 and 65%, respectively, of the doses given by gavage. The bioavailability of I in 2-month-old mice averaged 48 and 39% (diet) and 44 and 59% (gavage) of the 50- and 1350-mg/kg doses, respectively. In 2-month-old rats, absorption of the total radioactivity averaged 41% of the 50-mg/kg dose given in the diet. In 2- and 15-month-old rats, minimum absorption of the 1350-mg/kg dose averaged 36 and 45% (diet) and 51 and 71% (gavage), respectively; the minimum bioavailability averaged 20 and 29% (diet) and 39 and 44% (gavage), respectively. These studies demonstrate adequate absorption and bioavailability of I over a wide range of doses from the drug-diet mixtures and by young and old animals and also illustrate a useful experimental design for the estimation of relative oral absorption of a drug administered continuously in the diet over several days.