TURNOVER AND OXIDATION RATES OF PLASMA-FREE FATTY-ACIDS IN OBESE PATIENTS TREATED WITH DEXFENFLURAMINE

In order to assess a possible direct metabolic effect of dexfenfluramine (dF) apart from its action on food intake reduction, 10 obese postmenopausal women and 10 obese men (BMI = 32.19 +/- 1.99 kg/m2) were studied in a single-blind fashion: 4 weeks on placebo (D-28 to DO) and 4 weeks on dF (DO to D28). A balanced diet, computed on the basis of basal metabolic rate x 1.4, was followed throughout the study. The patients' alimentary diary was checked for compliance. FFA turnover and oxidation rate, using 1-C-14 palmitate intravenous infusion, was determined basally (D0), after single high-dose (30 mg, D1) and after long-term (15 mg b.i.d., D28) administration. Indirect calorimetric measurements were performed using a mass spectrometer, and the usual metabolic parameters were computed. The isotope method was used in order to assess plasma FFA oxidation (rate. Plasma FFA were analyzed by high-performance liquid chromatography (HPLC) and specific activity was determined at 55, 60, 65 and 70 min by counting dpm in HPLC eluates corresponding to the retention time of palmitate. The turnover rate was not significantly modified after single high-dose dF administration when compared to basal values (6.24 +/- 1.62 at D1 vs. 5.63 +/- 2.07 mmol/kg/min at DO), but was significantly increased at D28 compared with DO (6.35 +/- 1.96 mmol/kg/min; p < 0.05). A significant increase in FFA oxidation rate was observed with respect to basal values after dF administration both at D1 (0.81 +/- 0.33 at D1 vs. 0.61 +/- 0.21 mmol/kg/min at DO; p < 0.01) and at D28 (0.77 +/- 0.34 mmol/kg/min; p < 0.015). These results indicate a prompt action of the drug in activating FFA oxidation. Body weight loss was of the order of 0.6 kg after 28 days of diet plus placebo and about 3 kg during dF treatment. In conclusion, the increase of FFA oxidation due to a direct effect of dF can play an important role in the dF-induced weight loss.