SOFT - TIAFT 1998 Scientific Session 6 Thursday October 8, 1998
Click Picture Heesun Chung, Meejung Park, Wontak Jin and Youngchan Yoo

National Institute of Scientific Investigation, 331-1 Shinwol- dong, Yangchon-ku, Seoul, Korea 158-097

Fenfluramine, which is an anorectic agent, is widely abused as a diet pill in Korea. Because it is marketed freely in China, ethnic Koreans and tourists to China took it without knowing that it is controlled under the Act of Psychotropic agent in Korea. Because it's abuse is prevalent, there was a case in which a young mother who had taken it at a dose 6-10 times higher than recommended over an year, killed her one- year son in a state of mental disorder.

Fenfluramine is administered orally as the racemic mixture, but its optical isomers have different actions. d-Fenfluramine is used as an anorectic agent, while l-fenfluramine is a neuroleptic agent.

To investigate the metabolism of racemic fenfluramine, the urinary excretion of fenfluramine was studied in rats. The enanthiomeric separation of fenfluramine was achieved on achiral columns by gas chromatography using (S)-N-(trifluoroacetyl)-l-prolyl chloride as a derivatizing agent. The assay attempted to distinguish the chirality of fenfluramine after the administration of dl- fenfluramine to rats.

After administration of 15mg/kg of racemic fenfluramine, d-fenfluramine, l-fenfluramine and its metabolites d-norfenfluramine and l-norfenfluramine in urine were well resolved by chromatographic separation of TFP derivatives on DB-5 with retention times of 11.2, 11.8, 8.4, 8.6 min respectively. The amounts of d-fenfluramine were greater than l- fenfluramine, while d-norfenfluramine were smaller than l-norfenfluramine in urine. The ratio of d-norfenfluramine versus d-fenfluramine ranged from 0.6 to 2.8, while the ratio of l-norfenfluramine over l-fenfluramine was 6.9-17.2. This indicated that d-fenfluramine was metabolized at a slower rate than the l-isomer.

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