Gastrointestinal Dopamine Decarboxylase and Levodopa Pharmacokinetics

Overview

The main treatment for Parkinson's disease is a medication called levodopa. Levodopa has to be absorbed from the gut and travel to the brain to work, but a naturally occurring enzyme in the lining of the stomach, called dopamine decarboxylase (AADC), can break some of it down before it ever reaches the brain. We do not yet know whether people whose stomachs have more of this enzyme absorb less of their levodopa dose, have worsened gastrointestinal (GI) symptoms associated with levodopa intake, and whether that affects how well the medication controls their movement symptoms. This research may help doctors understand why levodopa works better in some people with Parkinson's disease than others, which could help improve treatment in future.

Patients will be asked to fast overnight prior to the study visit, including holding any doses of dopamine replacement therapy that they may be prescribed, including levodopa or equivalents, and any promotility agents, including cholinesterase inhibitors or peripherally-restricted dopamine antagonists (ie. Domperidone), that may impact gastric transit. At the start of the study visit, patients will undergo a neurological exam by a study investigator blinded to which study group the patient belongs. Exams will be performed according to the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, a validated clinical score of motor impairment in Parkinson's disease (PD). They will also undergo a baseline blood draw (5.5 mLs) through an indwelling venous cannula in the antecubital vein. Immediately afterwards, a single oral dose of levodopa (100 mg) obtained through the BIDMC research pharmacy with a standard volume of water (100 mL). Repeat blood samples will be collected immediately after oral levodopa ingestion (T=0) and then repeated every ½ hour until T=4 hours for a total of 10 draws, including the baseline. The initial placement of indwelling venous cannula will mitigate the necessity for repeated venipuncture during the study visit. At each ½ hour interval, additionally, patients will undergo repeat MDS-UPDRS-III assessments. After the 4-hour study concludes, the patient will be allowed to consume any food they would like and can resume home medications as previously prescribed clinically. Blood samples will be centrifuged to separate plasma and immediately frozen at -80oC until analysis by an investigator blinded to which study group the patient belongs. Separately, patients' prior clinically-obtained gastric biopsy blocks will be requested from BIDMC pathology (as otherwise discarded specimen) and stained for presence of AADC. This will not require any further time or visits from the patient themselves.