Kinetics of fenfluramine isomers in the rat

The kinetics of fenfluramine isomers were studied in the rat following oral doses of racemic fenfluramine. The data, analyzed using an analogue computer, indicate that the d-fenfluramine is metabolised and excreted at a slower rate than the 1-isomer, resulting in higher plasma and brain concentrations. The kinetic parameters of both isomers were dose-dependent. The rates of disappearance decreased as the dose was raised. The increase in brain area under the curves (AUC) was much greater than the increase of the dose. These findings suggested the rat has a limited capacity for disposition of fenfluramine.