Pipemidic acid: absorption, distribution, and excretion

Pipemidic acid was absorbed well by the oral route. Its peak levels in plasma ranged from 4 to 12 mug/ml at an oral dose of about 50 mg/kg in mice, rats, dogs, monkeys, and men. The protein binding of pipemidic acid was about 20% in dog plasma and about 30% in human serum. Pipemidic acid was distributed to most of the organs and tissues tested at the concentrations comparable to or higher than the plasma level. Its concentrations in bile and urine were much higher than the plasma level. About 25 to 88% of orally administered pipemidic acid was excreted into urine in a bacteriologically active form, the percentage depending on the Animals and doses employed. The remainder was excreted into feces in men. The main active principle in vivo was unchanged pipemidic acid itself. The mean lethal dose of pipemidic acid after a single oral dose was more than 16,000 mg/kg in mice. No abnormalities were observed in mice orally receiving pipemidic acid once a day for 4 weeks at doses of 1,000, 2,000, and 4,000 mg/kg per day, and in rats orally receiving the drug once a day for 2 weeks at doses of 400 and 1,600 mg/kg per day.