The invention relates to the treatment of neurodegenerative diseases such as Parkinson patients with motor complications in need of Continuous
Dopaminergic Stimulation. According to the invention a kit of pharmaceutical preparations is provided comprising
levodopa and an AADC-inhibitor.
Levodopa is applied via continuous subcutaneous infusion or by an oral modified release formulation and Continuous
Dopaminergic Stimulation is achieved by almost complete inhibition of the
peripheral levodopa metabolism. To reach far-going blockage of
levodopa metabolism, an AADC-inhibitor (e.g.,
benserazide,
carbidopa) is given orally in a much higher than normal
dose and, as an indispensable prerequisite, the AADC-inhibitor has to be applied evenly distributed over the day. e.g., via a Modified Release formulation. In order to prevent levodopa conjugation over the COMT pathway, an oral COMT-inhibitor (e.g., opicapone) is also added. In addition, a
drug-
drug-interaction between the AADC-inhibitor and opicapone further increasing the activity of the former is likely to occur. The resulting effective inhibition of
peripheral levodopa
metabolism allows a marked reduction of the necessary (equivalent) levodopa (or
prodrug) doses to 300-600 mg / day, which is, however, sufficient to reach high levodopa
plasma levels of 1500 to 3000 ng / ml. The low daily levodopa
dose is infused subcutaneously via minipump and is well-tolerated at the
infusion site. Alternatively, the low daily levodopa
dose is provided as an oral modified release formulation. The high steady-state levodopa
plasma levels reached, allow effective Continuous
Dopaminergic Stimulation-therapy for Parkinson's
disease patients of any degree of severity. As additional benefit, the largely complete AADC-inhibition prevents the
peripheral generation of
dopamine and the cumbersome
dopaminergic adverse effects (e.g.,
nausea, cardiovascular and
gastro-intestinal adverse effects) are prevented.