PHARMACOKINETICS AND PHARMACODYNAMICS OF (-THREO-METHYLPHENIDATE ENANTIOMER IN PATIENTS WITH HYPERSOMNIA())

The pharmacokinetics of (+)-methylphenidate after oral administration of 20 mg racemic methylphenidate hydrochloride and the relationship be tween clinical effects of plasma (+)-methylphenidate concentration wer e investigated in 15 patients with hypersomnia and four healthy volunt eers. The elimination half-life of (+)-methylphenidate in patients was within the range of 2.6 to 3 hours, and the time to reach the peak co ncentration ranged from 1 to 3 hours. The values of half-life and time to reach the peak concentration in the patients were almost the same as the values in healthy subjects. The plasma (+)-methylphenidate conc entration profiles after repeated administration of racemic methylphen idate were similar to those after single administration. No correlatio n was observed between the plasma (+)-methylphenidate concentration an d the subjective sleepiness as measured by Stanford Sleepiness Scale. On the other hand, a significant correlation was found between the sle ep latency as measured by the multiple sleep latency test and the plas ma concentrations of (+)-methylphenidate (r = 0.850). The time course of the sleep latency after repeated administration was similar to that after single administration. The sleep latency of more than 10 minute s was achieved by maintaining the plasma (+)-methylphenidate concentra tions above 3 ng/ml.