Why do ‘OFF’ periods still occur during continuous drug delivery in Parkinson’s disease?

Table 4 Possible reasons for persistence of ‘OFF’ periods in continuous drug delivery therapies

Reasons for ‘OFF’ periods	Rotigotine	LCIG	CSAI
Drug- or Device-related
Dose/Time	✓	✓	✓
Pump Failure	×	✓	✓
Line Blockage	×	✓	✓
Patch adhesion	✓	×	×
Tube/needle displacement/migration	×	✓	✓
Fibrosis/adhesion	×	✓	✓
Site-specific
Local Peritonitis	×	✓	×
Sub-absorption	×	✓	×
H. Pylori infection	×	✓	×
Gastritis	×	✓	×
Duodenitis	×	✓	×
Small intestinal bacterial overgrowth	×	✓	×
Protein-rich meals or fasting	×	✓	×
Constipation	×	✓	×
Skin conditions/skin nodules	✓	×	✓
Central or Disease-related
Brain penetration	?	?	?
Conversion to dopamine	×	✓	×
DA receptors stimulation	✓	✓	✓
Non-DA binding	?	?	?
Presynaptic storage	×	✓	×
Loss of long-duration response	✓	✓	×
Involvement of non-dopaminergic pathways	?	?	?
Others
Infection (e.g., urinary tract infection)	✓	✓	✓
Emotional stressor	✓	✓	✓
Diurnal (circadian) pattern	?	✓	?

LCGI levodopa-carbidopa intestinal gel, CSAI continuous subcutaneous apomorphine infusion

ISSN: 2047-9158