Levodopa in the treatment of Parkinson's
Levodopa (L-dopa) is a common drug administered during the progressive stages of PD. L-dopa is considered a prodrug, meaning it is not activated until after it crosses the blood brain barrier via active transport. The primary use of Levodopa is to restore depleted levels of dopamine at the presynaptic terminal of the substantia nigra, which restores functional movement. This replacement can relieve symptoms of PD, such as freezing and rigidity. If a tolerance is built up to L-dopa, or adverse motor effects become present with this drug alone, partner drugs Benserazide and Carbidopa (LD-CD) can be supplemented to prevent the further premature breakdown in the periphery.
Optimal oral dosing of LD-CD is typically between 97.5 mg-390 mg for a single dose, and 25mg-100mg bi-daily/tri-daily for either sustained release or immediate release. The volume of distribution is typically around 28.5 L and the plasma half-life clearance is 1.8 hours. Therefore, frequent dosage is required. The renal clearance of L-dopa is approximately 72 ml/min.
Many of the adverse effects that are present with Levodopa are due to the fact that it is not combined with a partner drug. Some of the most common adverse effects to be aware of during a physical therapy visit include gastrointestinal distress due to the enteral administration, cardiac difficulties, gait disturbances due to dyskinesias, end of dose akinesia, and a tolerance after around 3-4 years. Administering physical therapy treatment during the peak time of this drug helps to avoid these end of dose side effects.
- Standaert DG, Roberson ED. Chapter 22: Treatment of Central Nervous System Degenerative Disorders. In: Goodman & Gilman's: The Pharmacological Basis of Therapeutics. Vol 1. 12th ed. New York, NY: The McGraw-Hill Companies, Inc. ; 2011.1.
- Lewitt MD, PA. Levodopa therapy for Parkinsons disease: Pharmacokinetics and pharmacodynamics. Movement Disorders. 2014;30(1):65-67. doi:10.1002/mds.26082.
- Connolly MD, BS, Lang MD, AE. Pharmacological Treatment of Parkinson Disease. Jama. 2014;311(16):1670. doi:10.1001/jama.2014.3654.
- del Amo EM, Urtti A, Yliperttula M. Pharmacokinetic role of L-type amino acid transporters LAT1 and LAT2. European Journal of Pharmaceutical Sciences. 2008;35(3):161-174. doi:10.1016/j.ejps.2008.06.015
- Hsu PhD, A, Yao PhD, H-M, Gupta PhD, S, Modi PhD, NB. Comparison of the pharmacokinetics of an oral extended-release capsule formulation of carbidopa-levodopa (IPX066) with immediate-release carbidopa-levodopa (Sinemet®), sustained-release carbidopa-levodopa (Sinemet® CR), and carbidopa-levodopa-entacapone. The Journal of Clinical Pharmacology. 2015;55(9):996. doi:10.1002/jcph.514.