RESUMO
The distribution, metabolism, and elimination kinetics at two different doses of phenobarbital were examined in rats. After intravenous injection, phenobarbital distributed very rapidly to the liver and kidneys, less rapidly to the muscle and gut, and much more slowly to the brain. At the higher dose, a concentration rebound was observed 1 hr after injection. In addition, phenobarbital distributed unevenly in various organs as a result of a different extent of drug binding. A physiologically based model, including enterohepatic cycling and diffusion resistances between blood and tissue, is proposed for phenobarbital pharmacokinetics. It satisfactorily describes phenobarbital distribution in rats at the two doses and allows an evaluation of fundamental physicobiochemical parameters such as drug-tissue binding constants, blood-tissue transport coefficients, metabolism, and elimination rate constants.
