Carbidopa

Backround: Parkinson's disease is a pathology involving the progressive degeneration of dopaminergic neurons in the substantia nigra of the brain. L-DOPA combined with an inhibitor of DOPA decarboxylase, a pyridoxal 5'-phosphate-dependent enzyme, is still the most effective treatment for symptoms of Parkinson's disease. LDOPA increases synaptic dopamine, while the inhibitor of peripheral DOPA decarboxylase reduces the conversion of L-DOPA to dopamine in the systemic circulation, allowing for greater L-DOPA distribution into the central nervous system. CarbiDOPA and benserazide are the inhibitors currently used in Parkinson's disease treatment. However, carbiDOPA and trihydroxybenzylhydrazine, the active metabolite of benserazide, are substrate analogues both endowed with a hydrazine function, which irreversibly bind not only to DDC but also to free pyridoxal 5'-phosphate and pyridoxal 5'-phosphate-dependent enzymes. Therefore, the lack of DOPA decarboxylase specificity, responsible for various side effects and adverse reactions, is a negative factor in such treatment of the disease.

Patients with Parkinson's disease often have a good initial response to dopaminergic therapy but later usually develop motor fluctuations and dyskinesia. In these patients, continuous infusion of levodopa-carbidopa intestinal gel (LCIG) allows for maintaining adequate dopamine levels and for improving motor and nonmotor symptoms, as well as quality of life and autonomy. Adequate candidate selection and follow-up are crucial for treatment success. Management should be multidisciplinary, and patient and caregiver education is a priority. This expert consensus document has been developed by a team of neurologists, gastroenterologists and nurses who have a vast experience in LCIG therapy, with an intention to provide knowledge and tools to facilitate patient management throughout all phases of LCIG treatment process.

Parkinson disease (PD) is a slowly progressive, incurable, neurodegenerative disorder with progressive motor symptoms that can be managed with treatments. Levodopa is generally recognized as the most effective and widely used treatment for PD. It improves function and quality of life, morbidity, and mortality, and therefore reduces individual and societal costs. Levodopa has a relatively short half-life, however, and is quickly metabolized in the plasma, leading to fluctuations, including wearing-off of effect and inconsistent symptomatic relief as well as development of dyskinesias, with both wearing off and dyskinesias worsening with advancing disease. Immediate-release and controlled-release formulations have been used with success, but motor fluctuations remain a problem. RYTARY (levodopa and carbidopa, IPX066) is an oral extended-release therapy composed of carbidopa-levodopa microbeads designed to dissolve at various rates that allows for quick absorption and sustained levodopa release over an extended period.

A discussion between Dr. Dee Silver and Dr. Richard Trosch provides insight and advice for physicians considering a switch from immediate-release carbidopa-levodopa (IR CD-LD) to RYTARY as a treatment for patients with Parkinson disease (PD). The dialogue describes how they identify patients with PD who may and may not be successful switching to RYTARY, how they approach the conversion process and patient compliance, and how they address some side effects that may occur after patients begin taking RYTARY. The clinicians also discuss their experiences with how long it takes to establish a stable regimen as well as provide general advice regarding conversion from treatment with IR CD-LD to RYTARY.