COMPARISON BETWEEN A FAST AND A SLOW-RELEASE PREPARATION OF LEVODOPA AND A COMBINATION OF THE 2 - A CLINICAL AND PHARMACOKINETIC STUDY

After overnight drug withdrawal and in the fasting state, 11 patients with Parkinson's disease (PD) and a fluctuating response to chronic le vodopa treatment were given, in random sequence on consecutive days, e quivalent levodopa doses (with peripheral decarboxylase inhibitor) (a) as levodopa methyl ester (ME), (b) as Sinemet CR, or (c) as half the dose of ME together with a halved tablet of Sinemet CR. All patients t urned ON rapidly after treatments a and c, but only half did so after treatment b. On period duration was longest after treatment c, interme diate after treatment a, and shortest after treatment b. Pharmacokinet ic analysis in a subset of 6 patients revealed no significant differen ce between treatments a and c, although there was a trend for t(1/2), to be longer after treatment c. We conclude that giving ME with a halv ed tablet of Sinemet CR provided a useful clinical balance between rap id onset and extended duration of action of at least the first levodop a intake of the day. In view of differing release profiles between who le and halved tablets of Sinemet CR, similar single-dose pharmacokinet ic studies, followed by sequential-dose clinical studies, are indicate d when Sinemet CR 125 tablets soon become available.