DIFFERENT ADMINISTRATION SCHEDULES OF THE SAME DOSE OF 2,5-HEXANEDIONE INFLUENCE THE DEVELOPMENT OF NEUROPATHY AND THE TOXICOKINETICS

The same total dose (1.2 g/kg/week) of 2,5-hexanedione (2,5-HD) was ad ministered subcutaneously at 100 mg/kg/12 hr, 200 mg/kg/24 hr, and 400 mg/kg/48 hr to three groups of Donryu rats. The peripheral neuropathy induced by 2,5-HD was confirmed by clinical observation every day, an d neurophysiological measurements every 4 weeks. During the 15th week of this experiment, 2,5-HD concentrations in plasma 0.5 to 24 hours af ter injection were determined. It was found that the greater the dose of 2,5-HD per treatment injected, the earlier peripheral neuropathy de veloped. Toxicokinetic analysis showed that both the values of the are a under the plasma concentration versus time curve and the half life o f 2,5-HD were increased, but the excretion parameters (Ke) were decrea sed, in animals treated with 200 mg/kg/24 hr and 400 mg/kg/48 hr 2,5-H D.