Factors that may effect the reduction of hunger and body weight following d-fenfluramine administration.

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.