Profile of inhaled levodopa and its potential in the treatment of Parkinson’s disease: evidence to date

Abstract

Inhaled levodopa is a newly emerging therapeutic option in the treatment of “off ” symptoms associated with Parkinson’s disease (PD). Its mode of delivery offers more rapid absorption of levodopa and shorter onset of clinical benefit compared to oral formulations, and has been shown to be feasible for use in patients with PD experiencing worse motor function due to declining plasma levodopa levels. Clinical development of this compound is supported by preclinical, Phase I–III, long-term-safety studies and studies in special populations, including otherwise-healthy asthmatics and smokers. These investigations demonstrated that the drug is well tolerated without risk of long-term (up to 1 year) changes in pulmonary function or spirometry measures. The most common side effects among PD patients were a mild cough, upper respiratory tract infection, nausea, sputum discoloration, and dyskinesia. Inhaled levodopa offers a different administration method and side-effect profile from the currently available options for rescue therapy for Off periods in PD, though comparative studies have not been performed. The drug is presently under review by the US Food and Drug Administration.

<p>Profile Of Patients With Advanced Parkinson’s disease Suitable For Device-Aided Therapies: Restrospective Data Of A Large Cohort Of Romanian Patients</p>

“…[14][15][16] Clinical studies evaluating the efficacy of inhaled LD may bring new data into this context. 17 It cannot be confirmed at this time whether the magnitude of the clinical benefit of these preparations (used mainly in patients with moderate PD severity) is fully reproduced in APD. However, their value may be increasingly appreciated by the patients who will not accept DAT.…”

<p>Levodopa-Carbidopa Intestinal Gel Infusion Therapy Discontinuation: A Ten-Year Retrospective Analysis of 204 Treated Patients</p>

“…[19][20][21] Clinical studies evaluating the efficacy of inhaled LD showed its efficiency regarding the reduction of motor fluctuations that usually accompany standard preparations. 22 The continuous delivery of LCIG directly into the proximal small intestine via percutaneous endoscopic gastro-jejunostomy (PEG-J) provides more stable plasma concentrations of LD. 1,23,24 This reduces motor response fluctuations and has also been shown to improve non-motor complaints commonly associated with chronic oral LD therapy.…”

Intrinsic Auricular Muscle Zone Stimulation Improves Walking Parameters of Parkinson's Patients Faster Than Levodopa in the Motion Capture Analysis: A Pilot Study

“…Oral medications have a latency of up to 90 min to demonstrate symptomatic relief in pace-related gait parameters in PD, and new therapeutic approaches have been tried to overcome this off period of oral medications (28,29). Inhaler levodopa is one of the approaches to overcome this off period and has been shown to have a faster onset compared to oral medications for PD (28,29). However, such inhaler options do not eliminate the long-term risks of levodopa usage and the resulting narrow therapeutic window with increased side effects, including dyskinesia (1)(2)(3).…”

“…Compared to the sole-medication group, the sole-stimulation group demonstrated not only a significant effect but also a faster onset. Oral medications have a latency of up to 90 min to demonstrate symptomatic relief in pace-related gait parameters in PD, and new therapeutic approaches have been tried to overcome this off period of oral medications ( 28 , 29 ). Inhaler levodopa is one of the approaches to overcome this off period and has been shown to have a faster onset compared to oral medications for PD ( 28 , 29 ).…”