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[1]. The primary use of Levodopa is to restore depleted levels of dopamine at the presynaptic terminal of the substantia nigra, which restores functional movement[2]. This replacement can relieve symptoms of PD, such as freezing and rigidity[3]. 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[4].

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[5]. 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[2].

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.[3]


  1. 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.  
  2. 2.0 2.1 Lewitt MD, PA. Levodopa therapy for Parkinsons disease: Pharmacokinetics and pharmacodynamics. Movement Disorders. 2014;30(1):65-67. doi:10.1002/mds.26082.
  3. 3.0 3.1 Connolly MD, BS, Lang MD, AE. Pharmacological Treatment of Parkinson Disease. Jama. 2014;311(16):1670. doi:10.1001/jama.2014.3654.
  4. 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
  5. 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.