The Drug Delivery System
The first studies of intravenous and intraduodenal infusions of levodopa utilized water solutions of levodopa. The chemical properties of levodopa and carbidopa require large volumes of water for preparing one day s supply, which made the method laborious.⁷ This problem was addressed with the development of a levodopa/carbidopa gel (Duodopa®, Solvay Pharmaceuticals GmbH, Hannover, Germany). By using a gel of carboxymethylcellulose (2.92% carmellose sodium), the concentration of levodopa is 20mg/ml, making a cassette containing 100ml enough for one day s use for most patients. The cassette is attached to a portable pump (CADD-Legacy-Duodopa, Smiths Medical, MN, US). The tube of the cassette is connected to a percutaneous endoscopic gastrostomy (PEG) tube, containing a smaller-bore intestinal tube inside (Bengmark tube, Nutricia, Switzerland). The intestinal tube is placed beyond the pylorus to allow for immediate absorption across the intestinal mucosa in the duodenum or proximal jejunum. A nasoduodenal tube may be used during a test period to avoid unnecessary surgery.

Dosage
Initial dosage of the levodopa/carbidopa gel is calculated based on the previous dose of oral levodopa or levodopa equivalents. The dose is usually between 20 and 120mg/h depending on the individual patient s requirements. An individual morning bolus dose, usually 40 200mg levodopa, is always used to rapidly reach steady state, from which the concentration can be kept constant by the individualized infusion rate. Both morning dose and infusion rate are fine-tuned over the course of the first few days to find the optimal dose that produces a continuous on state without troublesome dyskinesia. Adjustments of the infusion rate can be made in small increments of 2mg/h. The patient is discharged from the hospital after PEG surgery is completed, an optimal dose is found, and the patient or a relative has learned how to handle the infusion system. This usually takes about one week. Follow-up should be carried out by a PD-specialized nurse or at an outpatient visit a few weeks later. Dosage may need to be adjusted after weeks to months, probably due to longterm plastic changes in the brain. The levodopa/carbidopa infusion has mostly been used as monotherapy, which is practical, but it may be combined with other anti-Parkinsonian drugs, especially for non-dopaminergic symptoms.