Actively Transported Levodopa Prodrug XP21279

LeWitt, Peter A.; Ellenbogen, Aaron; Chen, Dan; Lal, Ritu; McGuire, Kristin; Zomorodi, Katie; Luo, Wendy; Huff, F. Jacob

doi:10.1097/wnf.0b013e31824e4d7d

Cited by 33 publications

(5 citation statements)

References 17 publications

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“…The aim of this formulation is to provide a better absorption profile, extending the delivery of LD. XP21279-CD (XP21279-CD) formulation contains 241 mesylate salt, equivalent to 104 mg LD, and CD 25 mg, and has a relative bioavailability of 88.2% of that of IR CD/LD [110, 111]. A phase 1b open-label two period trial was designed to evaluate pharmacokinetic and pharmacodynamics properties of XP21279-CD [110].…”

Section: Levodopa Formulations: Oral Routementioning

confidence: 99%

“…Considering that patients already had motor fluctuations at recruitment, new or worsening dyskinesias were more commonly experienced with XP21279-CD (21%) compared to IR CD/LD (14%). All other adverse events, mild or moderate in intensity, such as headache, insomnia, somnolence, gastro-oesophageal reflux, had similar prevalence with both treatments [110]. To-date no plans for future developments of XP21279 have been declared.…”

Section: Levodopa Formulations: Oral Routementioning

confidence: 99%

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Levodopa in Parkinson’s Disease: Current Status and Future Developments

2018

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Section: Levodopa Formulations: Oral Routementioning

confidence: 99%

Section: Levodopa Formulations: Oral Routementioning

confidence: 99%

Levodopa in Parkinson’s Disease: Current Status and Future Developments

2018

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“…For IR CD-LD, Lewitt et al reported that the mean (SD) time to “on”, as assessed via patient diary, was 0.95 (0.55) hours. 21 Similarly, Merims et al reported that the mean (SD) time to beginning of an “on” state after levodopa dosing, as judged by the patient, was 46 (21) minutes. 22 The original study did not use a stopwatch method to measure time to “on” and its duration.…”

Section: Discussionmentioning

confidence: 93%

Onset and duration of effect of extended-release carbidopa-levodopa in advanced Parkinson’s disease

Hauser¹,

Ellenbogen²,

Khanna³

et al. 2018

NDT

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BackgroundIn patients with Parkinson’s disease (PD), oral dosing of extended-release carbidopa-levodopa (Rytary, IPX066 [ER CD-LD]) achieves peak levodopa plasma concentrations within 1 hour and maintains them for 4–6 hours.AimsTo compare the onset and duration of ER CD-LD benefit with those of immediate-release carbidopa-levodopa (IR CD-LD) in PD patients with motor fluctuations, using crossover data, and to evaluate which threshold values of improvement in finger-tapping and Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores yield results most similar to those for trained raters’ “on”/“off” assessments.MethodsPatients underwent serial “on”/“off” rating and provided serial finger-tapping and UPDRS motor scores after receiving, in an “off” state, their usual morning IR dose or an ER dose designed to produce a similar levodopa peak concentration. Predefined improvement thresholds for analysis were 10%, 15%, and 20% increases in finger-tapping score and 2.5, 5, 7, and 11-point decreases in UPDRS motor score. Serial plasma samples were assayed for levodopa.ResultsAmong 27 patients, mean time to onset of an “on” state was similar for ER compared with IR CD-LD (0.83 vs 0.81 hour), but mean duration was significantly longer for ER CD-LD than for IR CD-LD (5.56 vs 2.69 hours; P<0.0001). Duration was best matched by a $20% improvement in finger-tapping, a $11-point improvement in UPDRS motor score, and a levodopa plasma concentration $1,000 ng/mL.ConclusionFor ER CD-LD, observer assessments of “on” state were corroborated by sustained treatment effects. Correlations among “on”-state duration, finger-tapping score, and UPDRS motor score may suggest clinically relevant thresholds for acute assessment of treatment benefit.

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“…Other approaches to improve pharmacokinetic parameters include the use of extended-release formulations of levodopa [ 288 , 289 , 290 ], the administration of levodopa gastric retention formulation [ 282 ] and the combination of immediate- and extended-release formulations with gastric retention [ 283 ].…”

Section: Therapeutic Optionsmentioning

confidence: 99%

Levodopa-Induced Dyskinesias in Parkinson’s Disease: An Overview on Pathophysiology, Clinical Manifestations, Therapy Management Strategies and Future Directions

Biase

Pecoraro

Carbone

et al. 2023

JCM

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Since its first introduction, levodopa has become the cornerstone for the treatment of Parkinson’s disease and remains the leading therapeutic choice for motor control therapy so far. Unfortunately, the subsequent appearance of abnormal involuntary movements, known as dyskinesias, is a frequent drawback. Despite the deep knowledge of this complication, in terms of clinical phenomenology and the temporal relationship during a levodopa regimen, less is clear about the pathophysiological mechanisms underpinning it. As the disease progresses, specific oscillatory activities of both motor cortical and basal ganglia neurons and variation in levodopa metabolism, in terms of the dopamine receptor stimulation pattern and turnover rate, underlie dyskinesia onset. This review aims to provide a global overview on levodopa-induced dyskinesias, focusing on pathophysiology, clinical manifestations, therapy management strategies and future directions.

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Actively Transported Levodopa Prodrug XP21279

Abstract: 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.

Cited by 33 publications

References 17 publications

Levodopa in Parkinson’s Disease: Current Status and Future Developments

Levodopa in Parkinson’s Disease: Current Status and Future Developments

Onset and duration of effect of extended-release carbidopa-levodopa in advanced Parkinson’s disease

Levodopa-Induced Dyskinesias in Parkinson’s Disease: An Overview on Pathophysiology, Clinical Manifestations, Therapy Management Strategies and Future Directions

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Actively Transported Levodopa Prodrug XP21279

Abstract: 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.

Cited by 33 publications

References 17 publications

Levodopa in Parkinson’s Disease: Current Status and Future Developments

Levodopa in Parkinson’s Disease: Current Status and Future Developments

Onset and duration of effect of extended-release carbidopa-levodopa in advanced Parkinson&rsquo;s disease

Levodopa-Induced Dyskinesias in Parkinson’s Disease: An Overview on Pathophysiology, Clinical Manifestations, Therapy Management Strategies and Future Directions

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Product

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Onset and duration of effect of extended-release carbidopa-levodopa in advanced Parkinson’s disease