some patients fluctuate unpredictably between mobility and
immobility ("the on-off effect"). "On" periods are usually
associated with high plasma levodopa concentrations and
often include abnormal involuntary movements, i.e.,
dyskinesias. "Off" periods have been correlated with low
plasma levodopa and bradykinetic episodes.
In an effort to reduce the occurrence of "wearing off"
and "on-off" phenomena, a controlled release oral dosage
combination was introduced with claims of slow and
simultaneous release of carbidopa and levodopa from the
formulation (US Patent Number 4,900,755 issued February 13,
1990). Data from clinical trials cited in the patent
indicate that effective antiparkinson effects were achieved
with fewer daily doses of the controlled release form as
compared with the conventional combination.
2. The specification goes on to say (page 2,
lines 12-22):
Nevertheless, there remains a significant flaw in the
therapeutic application of controlled release carbidopa-
levodopa; that is the considerable delay in onset of action.
Mean time to peak concentration in healthy elderly subjects
was found to be two hours for controlled release carbidopa-
levodopa and only 0.5 hours for the conventional form
(Physicians Desk Ref., 47th Ed., p. 976, 1993 [copy in the
record]). A controlled release dosage form that could also
provide rapid onset of action, at least equivalent to that
of conventional carbidopa-levodopa would have an obvious
clinical advantage over current therapy.
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