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Pharmacokinetic considerations for the use of levodopa in the treatment of Parkinson disease: focus on levodopa/carbidopa/entacapone for treatment of levodopa-associated motor complications.
Clin Neuropharmacol. 2013 May-Jun; 36(3):84-91.CN

Abstract

Parkinson disease (PD) is a progressive, disabling, neurodegenerative disorder characterized by both motor and nonmotor symptoms. Monoamine oxidase B inhibitors, dopamine agonists, N-methyl-D-aspartate antagonists and levodopa (LD), with its various formulations and administration modes, mainly improve the motor symptoms in PD, which are thought to be related to decreased dopamine levels in the brain. Of these therapeutic drug options, LD represents the most effective and best tolerated compound when it is administered several times a day. Pharmacokinetic trials of oral LD/dopa decarboxylase inhibitor (DDCI) formulations with and without the catechol-O-methyltransferase inhibitor, entacapone, showed that repeated administration with entacapone causes an increase in both the maximum concentration (Cmax) and time to Cmax (Tmax) of LD. In addition, gastrointestinal motility may also impact plasma LD behavior. These peripheral components of LD metabolism contribute to the onset of motor complications, which are predominantly associated with LD/DDCI owing to its short plasma half-life. The increase in Tmax is related to a slower increase in plasma LD concentrations after repeated LD/DDCI intake, which may also increase the risk of wearing off. An elevation in Cmax after reiterated LD intake increases the risk of peak-dose dyskinesia. Therefore, it may be useful to start with higher doses of LD formulations in the morning and then to titrate with different LD doses during the day according to the individual patient's motor behavior, which is particularly characterized by the onset of motor complications, such as off periods and dyskinesia, in more advanced stages of PD.

Authors+Show Affiliations

Department of Neurology, St Joseph Hospital Berlin-Weissensee, Berlin, Germany. th.mueller@alexius.de

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

23673910

Citation

Müller, Thomas. "Pharmacokinetic Considerations for the Use of Levodopa in the Treatment of Parkinson Disease: Focus On Levodopa/carbidopa/entacapone for Treatment of Levodopa-associated Motor Complications." Clinical Neuropharmacology, vol. 36, no. 3, 2013, pp. 84-91.
Müller T. Pharmacokinetic considerations for the use of levodopa in the treatment of Parkinson disease: focus on levodopa/carbidopa/entacapone for treatment of levodopa-associated motor complications. Clin Neuropharmacol. 2013;36(3):84-91.
Müller, T. (2013). Pharmacokinetic considerations for the use of levodopa in the treatment of Parkinson disease: focus on levodopa/carbidopa/entacapone for treatment of levodopa-associated motor complications. Clinical Neuropharmacology, 36(3), 84-91. https://doi.org/10.1097/WNF.0b013e31828f3385
Müller T. Pharmacokinetic Considerations for the Use of Levodopa in the Treatment of Parkinson Disease: Focus On Levodopa/carbidopa/entacapone for Treatment of Levodopa-associated Motor Complications. Clin Neuropharmacol. 2013 May-Jun;36(3):84-91. PubMed PMID: 23673910.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetic considerations for the use of levodopa in the treatment of Parkinson disease: focus on levodopa/carbidopa/entacapone for treatment of levodopa-associated motor complications. A1 - Müller,Thomas, PY - 2013/5/16/entrez PY - 2013/5/16/pubmed PY - 2014/8/6/medline SP - 84 EP - 91 JF - Clinical neuropharmacology JO - Clin Neuropharmacol VL - 36 IS - 3 N2 - Parkinson disease (PD) is a progressive, disabling, neurodegenerative disorder characterized by both motor and nonmotor symptoms. Monoamine oxidase B inhibitors, dopamine agonists, N-methyl-D-aspartate antagonists and levodopa (LD), with its various formulations and administration modes, mainly improve the motor symptoms in PD, which are thought to be related to decreased dopamine levels in the brain. Of these therapeutic drug options, LD represents the most effective and best tolerated compound when it is administered several times a day. Pharmacokinetic trials of oral LD/dopa decarboxylase inhibitor (DDCI) formulations with and without the catechol-O-methyltransferase inhibitor, entacapone, showed that repeated administration with entacapone causes an increase in both the maximum concentration (Cmax) and time to Cmax (Tmax) of LD. In addition, gastrointestinal motility may also impact plasma LD behavior. These peripheral components of LD metabolism contribute to the onset of motor complications, which are predominantly associated with LD/DDCI owing to its short plasma half-life. The increase in Tmax is related to a slower increase in plasma LD concentrations after repeated LD/DDCI intake, which may also increase the risk of wearing off. An elevation in Cmax after reiterated LD intake increases the risk of peak-dose dyskinesia. Therefore, it may be useful to start with higher doses of LD formulations in the morning and then to titrate with different LD doses during the day according to the individual patient's motor behavior, which is particularly characterized by the onset of motor complications, such as off periods and dyskinesia, in more advanced stages of PD. SN - 1537-162X UR - https://www.unboundmedicine.com/medline/citation/23673910/Pharmacokinetic_considerations_for_the_use_of_levodopa_in_the_treatment_of_Parkinson_disease:_focus_on_levodopa/carbidopa/entacapone_for_treatment_of_levodopa_associated_motor_complications_ L2 - https://doi.org/10.1097/WNF.0b013e31828f3385 DB - PRIME DP - Unbound Medicine ER -