Three studies have been undertaken to investigate why there are individual differences in the response to d-
fenfluramine with respect to food intake and hunger in the short term and on
body weight loss in the long term.
Fenfluramine and
norfenfluramine plasma levels have been used as probes to help detect and normalize these variances. In a single dose ranging volunteer study (0, 30, 40, and 60 mg), d-
fenfluramine levels were significantly related to caloric intake and hunger rating scales when compared individually, and the slopes of the regression lines showed intersubject variation. These slopes, an index of each subject's response to
fenfluramine, appear to be related to both the percentage underweight and more weakly to the percentage
overweight. Those subjects at the extremes of weight showed a greater response to a given
drug level. In two placebo-controlled 3 month studies (30 mg/day), the variances in
weight loss were not explained by steady state
drug levels, the percentage
overweight, initial weight, duration of
obesity, or caloric intake even when
weight loss was normalized for differences in
drug levels. Age, however, was significantly related to
weight loss, with each additional 10 years increasing
weight loss by approximately 1 kg. If confirmed, the sensitivity of
fenfluramine anorexia may be an objective acute test of the central control of food intake. However, in long term clinical studies,
drug levels were only weakly related to
weight loss and other undefined factors seem to determine which patients responded better to
fenfluramine treatment.