Opinion
Video
Barriers to Levodopa Use in Parkinson Disease
Author(s):
Panelists discuss how pharmacokinetic challenges with oral levodopa formulations have led to the development of levodopa-based continuous subcutaneous infusion therapy as a less invasive and more personalized approach.
Video content above is prompted by the following:
Advancements in Levodopa-Based Continuous Subcutaneous Infusion Therapy: Executive Summary for Physicians
Pharmacokinetic Challenges With Oral Levodopa
Oral levodopa formulations face several pharmacokinetic limitations that have necessitated the development of subcutaneous delivery options:
- Short half-life: Levodopa’s 1- to 2-hour plasma half-life necessitates frequent dosing
- Erratic gastric emptying: Variable absorption due to unpredictable gastric transit
- Competition with dietary amino acids for intestinal and blood-brain barrier transport
- Narrow therapeutic window: Small range between efficacy and adverse effects
- OFF periods: Declining plasma levels between doses lead to symptom reemergence
- Pulsatile stimulation: Nonphysiological dopamine receptor stimulation contributes to motor complications
- Advanced disease complications: Gastric dysmotility increases as disease progresses
Benefits of Continuous Subcutaneous Infusion
The subcutaneous route addresses these challenges by:
- Providing stable plasma levodopa concentrations
- Bypassing gastrointestinal absorption issues
- Reducing motor fluctuations and OFF periods
- Enabling more precise, individualized dosing
- Offering a less invasive alternative to surgical interventions
These advancements allow for more personalized treatment approaches that can significantly improve quality of life for patients experiencing motor symptoms.
