Parkinson's disease was first described in 1817 by James Parkinson. Based on his observation of only six individuals, Parkinson accurately described the resting tremor and festinate gait, bradykinesia, and postural instability associated with the disease today. Parkinson's disease primarily affects people >50 years of age and causes progressive neurological degeneration, physical disability, and worsening quality of life.

Consequently, most currently available drugs aim to restore striatal dopamine signaling. This can be best reached by increasing the supply of dopamine with oral levodopa (L-dopa), but also by stimulating dopamine receptors directly using dopamine agonists, or by inhibiting the reuptake of endogenous dopamine. Unfortunately, mainly due to the short half-life of L-dopa and the erratic absorption of oral L-dopa (causing pulsatile dopaminergic stimulation) these treatment strategies become increasingly ineffective in the course of this disease, and motor complications may further reduce the quality of life in these patients.

When levodopa (L-dopa) is administered intravenously to patients with severe Parkinson's disease, a therapeutic response may be seen within a 1/2 hour. However, when the drug is administered orally in lower doses to less disabled patients, a delay of 1–2 weeks often occurs before motor deficits start to improve. Recent data from the Early versus Late Levodopa study suggest that maximum improvement at a fixed dosage may take ≤3 months to develop. A nonspecific feeling of well-being and reduced tiredness are often the first benefits to occur, followed by greater alacrity and less stiffness. Rest tremor is slower to improve, but may eventually disappear altogether and remain well controlled throughout the rest of the course of the malady. Gait, balance, and speech may also improve, but the effect is usually more modest and a decline is common after several years of sustained treatment.

Parkinson's disease is a progressive neurodegenerative disorder with prominent motor features. The cardinal motor signs, bradykinesia, rigidity, and tremor, are treated effectively by dopaminergic therapies. Levodopa is standard, and often initial, therapy for patients with this condition. However, with continued treatment, and as the disease progresses, the response to oral dopaminergic drugs becomes unstable and motor fluctuations emerge, including off periods (when medication effects wear off) and dyskinesia (dystonic or choreatic movements) (Slide 1). Risk factors for motor complications include younger age at disease onset, longer disease duration, higher levodopa dosage, and more severe motor symptoms.

A duodenal levodopa (L-dopa) and carbidopa infusion has been developed to stabilize plasma levels of L-dopa, in order to reduce existing motor response fluctuations. Stable plasma levels have been shown to reduce these fluctuations significantly. A constant duodenal infusion with an L-dopa solution can improve response fluctuations, however L-dopa has very poor solubility. Only in an acidic environment can L-dopa be dissolved in large volumes. To supply 1 day of infusion with the conventional L-dopa solution, ∼4–5 liters are necessary, an inconvenience to most patients. With L-dopa/carbidopa infusion, L-dopa and carbidopa are concentrated in a water-based gel-like suspension to 20 mg/mL, which has reduced the infusion volumes to <100 mL/day.