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Fenfluramine is a sympathomimetic amine, the pharmacologic activity of which differs somewhat from that of the prototype drugs of this class used in obesity, the amphetamines, in appearing to produce more central nervous system depression than stimulation.
The mechanism of action of Fenfluramine HCl is unclear but may be related to brain levels (or turnover rates) of serotonin or to increased glucose utilization. The antiappetite effects of Fenfluramine HCl are suppressed by serotonin-blocking drugs and by drugs that lower brain levels of the amine. Furthermore, decreased serotonin levels produced by selective brain lesions suppress the action of Fenfluramine HCl.
In a study of 20 normal males, fenfluramine increased glucose utilization, resulting in decreased blood glucose levels. Experimental work in animals suggested that increased glucose utilization activated the satiety center and decreased the activity of the feeding center. Perhaps by this mechanism Fenfluramine HCl inhibits appetite. The relationship between glucose utilization and serotonin has not been clarified.
Fenfluramine is well-absorbed from the gastrointestinal tract, and a maximal anorectic effect is generally seen after 2 to 4 hours. In man, fenfluramine is de-ethylated to norfenfluramine which is subsequently oxidized to m-trifluoromethyl benzoic acid and excreted as the glycine conjugate, m-trifluoromethylhippuric acid. Other compounds found in the urine include unchanged fenfluramine and norfenfluramine.
The rate of excretion of fenfluramine is pH dependent, with much smaller amounts appearing in an alkaline than in an acid urine.
The half-life of fenfluramine is said to be about 20 hours, compared with 5 hours for amphetamines; however, if urinary excretion is rapid and the pH maintained in the acidic range (below pH 5), half-life can be reduced to 11 hours. Fenfluramine and norfenfluramine reach steady state concentrations in plasma within 3 to 4 days following chronic dosage.
The greatest weight loss is seen in those patients who maintain the highest levels of Fenfluramine HCl. A 2-to-3-kg weight loss over 6 weeks is associated with a plasma level of 0.1 mcg/ml (or 10 mcg/100 ml).
Last reviewed on RxList: 12/8/2004
This monograph has been modified to include the generic and brand name in many instances.
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