Strengths and limitations of levodopa

Although levodopa has been a major success story for the management of PD, it does have some limitations, such as the development of dopa-related response fluctuations (both motor and non-motor) and drug-induced dyskinesias.⁴

A single dose of levodopa/decarboxylase inhibitor relieves symptoms for several hours.^4,9 Levodopa has a half-life of approximately 50 minutes once absorbed into the bloodstream, although the addition of a decarboxylase inhibitor extends the half-life to approximately 90 minutes.^9,10 Therefore, patients typically need to take their levodopa several times during the day to control their symptoms.⁹

The duration of therapeutic effect of levodopa doses often decreases over time, as the patient begins to experience greater periods of motor fluctuations and/or drug-induced dyskinesias.² From this point onwards, the patient experiences shorter periods of relief from motor symptoms, and greater periods of time with levodopa-induced complications, all of which can substantially impair the patient’s quality of life.^2,4

References:
1. Nutt JG, Fellman JH. Pharmacokinetics of levodopa. Clin Neuropharmacol 1984; 7 (1): 35–49.

2. Chapuis S, Ouchchane L, Metz O, et al. Impact of the motor complications of Parkinson’s disease on the quality of life. Mov Disord 2005; 20 (2): 224–230.

3. Freitas ME, Hess CW, Fox SH. Motor complications of dopaminergic medications in Parkinson’s disease. Semin Neurol 2017; 37 (2): 147–157.

4. Hametner E, Seppi K, Poewe W. The clinical spectrum of levodopa-induced motor complications. J Neurol 2010; 257 (Suppl 2): S268–S275.

5. Olanow CW, Stocchi F. Levodopa: A new look at an old friend. Mov Disord 2018; 33 (6): 859–866.

6. Cenci MA, Riggare S, Pahwa R et al. Dyskinesia matters. Mov Disord 2020; 35 (3): 392–396.

7. Ferreira JJ, Katzenschlager R, Bloem BR, et al. Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson’s disease. Eur J Neurol 2013; 20 (1): 5–15.

8. Sethi KD. The impact of levodopa on quality of life in patients with Parkinson disease. Neurologist 2010; 16 (2): 76–83.

9. Deleu D, Northway MG, Hanssens Y. Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson’s disease. Clin Pharmacokinet 2002; 41 (4): 261–309.

10. Hauser RA. Levodopa: Past, present, and future. Eur Neurol 2009; 62 (1): 1–8.