Pharmacokinetics of Etilevodopa Compared to Levodopa in Patient's With Parkinson's Disease: An Open-label, Randomized, Crossover Study

  title={Pharmacokinetics of Etilevodopa Compared to Levodopa in Patient's With Parkinson's Disease: An Open-label, Randomized, Crossover Study},
  author={Ruth Djaldetti and Nir Giladi and Sharon Hassin-Baer and H. Shabtai and Eldad Melamed},
  journal={Clinical Neuropharmacology},
“Dose failures” and “delayed on” phenomena following an intake of levodopa dose in patients with Parkinson's disease (PD) with motor fluctuations may be caused by stagnation of poorly soluble levodopa in the atonic stomach. Etilevodopa is a unique, highly soluble prodrug of levodopa. When ingested, etilevodopa is more readily dissolved in the stomach than levodopa. It passes unchanged through the stomach to the duodenum, where it is rapidly hydrolyzed by local esterases and rapidly absorbed as… 

A randomized controlled trial of etilevodopa in patients with Parkinson disease who have motor fluctuations.

Despite the theoretical pharmacokinetic advantage of etilevodopa, there was no improvement in TTON, response failures, or off time compared with levodopa.

Pharmacokinetic Optimisation in the Treatment of Parkinson’s Disease

  • D. Nyholm
  • Medicine, Biology
    Clinical pharmacokinetics
  • 2006
In general, initial dopamine receptor agonist monotherapy is associated with poorer motor performance and lower incidence of motor complications compared with levodopa, and CDS can be approached by optimising the use of dopaminergic drugs based on pharmacokinetic data.

Oral and Infusion Levodopa-Based Strategies for Managing Motor Complications in Patients with Parkinson’s Disease

A treatment algorithm is proposed that takes into account all currently available levodopa-based treatment strategies for motor complications in patients with PD and may stabilize and significantly improve motor function as well as patients’ quality of life.

Actively Transported Levodopa Prodrug XP21279: A Study in Patients With Parkinson Disease Who Experience Motor Fluctuations

XP21279 provided improved pharmacokinetic performance (highlighted by reduction in variability of LD concentration) compared with CD-LD and therefore may provide better control of PD motor fluctuations.

Dopamine and Levodopa Prodrugs for the Treatment of Parkinson’s Disease

LD ester prodrugs have demonstrated an adequate intranasal delivery of LD, thus enabling the absorption of therapeutic agents to the brain, and the future of utilizing pro drugs for the treatment of PD seems to be bright.

Treatment of motor fluctuations in Parkinson’s disease: recent developments and future directions

Clinical trials revealed diverse but promising results raising the possibility of new therapeutic modalities for PD in the near future, including duodenal infusion of a levodopa/carbidopa, new extended-release levodOPA and oral pro-levodopa forms.

Evaluating the Scope of Gastrointestinal Symptoms of Parkinson’s Disease: A Review of the Evidence

The main focus of this review is a discussion of the clinical presentation, evaluation, treatment options, pathology, and etiology of individual GI symptoms in humans.

Novel pharmacological strategies for motor complications in Parkinson’s disease

Novel strategies for pharmacological intervention with the use of nondopaminergic treatments, with drugs targeting selected transmitter receptors expressed on striatal neurons appear more promising, and hold the promise of providing effective control or reversal of motor response complications.

Bioavailability Enhancement: A Review

The techniques of Bioavailability enhancement for the attainment of effective absorption and improved bioavailability are described.



The pharmacokinetics of intravenous and oral levodopa in patients with Parkinson's disease who exhibit on-off fluctuations.

The data presented here are consistent with a two-compartment kinetic model, and it is not known whether the difference in pharmacokinetics is due to chronic therapy or whether it is specific to those patients who show on-off phenomena, but such changes might be related to the development of fluctuations in clinical response.

Levodopa ethylester : A novel rescue therapy for response fluctuations in parkinson's disease

It is suggested that subcutaneous and intramuscular administration of LDEE may be advantageous as a novel therapeutic strategy for response fluctuations and may be particularly useful to rapidly and predictably rescue patients from a variety of disabling “off” situations.

Clinical Pharmacokinetic and Pharmacodynamic Properties of Drugs Used in the Treatment of Parkinson’s Disease

No single best treatment exists for an individual patient with PD, and particularly in the advanced stage of the disease, treatment should be individually tailored.

Motor fluctuations in Parkinson's disease: Central pathophysiological mechanisms, part II

It is suggested that postsynaptic modifications, presumably at the receptor level, serve as the major determinant for the increasing difficulty with optimal dose adjustment and motor fluctuations, especially of the on‐off type, which complicate levodopa therapy of patients with advance Parkinson's disease.

Role of integrative pharmacokinetic and pharmacodynamic optimization strategy in the management of Parkinson"s disease patients experiencing motor fluctuations with levodopa.

  • C. Okereke
  • Medicine, Biology
    Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
  • 2002
It is worthy of mention that an integrated optimal pharmacological approach involving the peripheral, and central pharmacokinetics of levodopa as well as its central pharmacodynamics would ensure better treatment and management of this disease.

The influence of levodopa on gastric emptying in man.

The results indicate thatlevodopa inhibits gastric emptying and thus influences its own absorption and is the cause of the multiple plasma peaks commonly observed following oral levodopa.

Motor fluctuations in Parkinson's disease: Central pathophysiological mechanisms, Part I

The results support the view that progressive dopamine neuron degeneration reduces the brain's ability to buffer shifts in levodopa availability attending its periodic oral administration; the clinical result is wearing‐off phenomenon.

Longitudinal monitoring of the levodopa concentration‐effect relationship in Parkinson's disease

The data indicate that the duration of motor response becomes a major determinant of drug efficacy over years, and modifications in levodopa effect-compartment equilibration half-life and EC50 further support the suggestion that alterations in cerebrallevodopa kinetics have an important role in the development of response fluctuations.

Gastric emptying in Parkinson's disease

It is demonstrated that delayed gastric emptying is common in PD patients and is more marked in those with response fluctuations, which is an important target organ in PD.

Gastric emptying time and gastric motility in patients with Parkinson's disease

  • R. HardoffM. Sula Nir Giladi
  • Medicine, Psychology
    Movement disorders : official journal of the Movement Disorder Society
  • 2001
It is concluded that gastric emptying time in patients with PD was delayed compared with control volunteers and was even slower in patients treated with levodopa, when patients developed motor response fluctuation.