Comparison of the effectiveness, safety, and costs of anti-Parkinson drugs: A multiple-center retrospective study.

AIMS: This study aimed to systematically compare the effectiveness, safety, and costs of different anti-Parkinson drugs (APDs). METHODS: This is a multi-center study that retrospectively analyzed the data of 8420 outpatients with PD from 2014 to 2019 across 30 tertiary hospitals in China. The effectiveness was evaluated by changes in total dosages of APDs, normalized by levodopa equivalent dose (LED) and presented as ΔLEDs; levodopa equivalent dose cost (LEDc) represented the daily cost of APDs; and newly added diagnostics were represented as APDs-related adverse events. RESULTS: A total of 384 patients with eligible medical records for three consecutive years were enrolled. Patients treated with carbidopa/levodopa or levodopa/benserazide had significantly lower mean ΔLEDs than other groups (p < 0.01), followed by pramipexole and selegiline. The piribedil group had the highest ΔLEDs, with mean differences of 112.56-355.04 mg compared to other groups (p < 0.01). Meanwhile, LEDc in the levodopa/benserazide, carbidopa/levodopa, and piribedil groups were significantly lower than those in pramipexole or selegiline groups ($0.088-0.135/day for levodopa/benserazide; $0.070-0.126/day for carbidopa/levodopa; $0.112-0.138/day for piribedil; $0.290-0.332/day for pramipexole; $0.229-0.544/day for selegiline; p < 0.01). Patients with piribedil had more adverse events, with an incidence rate of 35.7%, followed by levodopa/benserazide (25.6%), selegiline (23.5%), carbidopa/levodopa (23.3%), and pramipexole (16.4%). Pramipexole showed a lower incidence rate of adverse events than piribedil, including neuropsychiatric symptoms (p = 0.006), headache/dizziness (p = 0.016), and gastrointestinal symptoms (p = 0.031). CONCLUSIONS: Carbidopa/levodopa or levodopa/benserazide might exhibit better clinical improvement with less medical cost, while piribedil presented less clinical improvement but a higher risk of headache/dizziness, gastrointestinal, and neuropsychiatric symptoms.

Quantitative Colorimetric Sensing of Carbidopa in Anti-Parkinson Drugs Based on Selective Reaction with Indole-3-Carbaldehyde.

The quality of life of patients affected by Parkinson's disease is improved by medications containing levodopa and carbidopa, restoring the dopamine concentration in the brain. Accordingly, the affordable quality control of such pharmaceuticals is very important. Here is reported the simple and inexpensive colorimetric quantification of carbidopa in anti-Parkinson drugs by the selective condensation reaction between the hydrazine group from carbidopa and the formyl functional group of selected aldehydes in acidified hydroalcoholic solution. An optical assay was developed by using indole-3-carbaldehyde (I3A) giving a yellow aldazine in EtOH:H2O 1:1 (λmax~415 nm) at 70 °C for 4 h, as confirmed by LC-MS analysis. A filter-based plate reader was used for colorimetric data acquisition, providing superior results in terms of analytical performances for I3A, with a sensitivity ~50 L g-1 and LOD ~0.1 mg L-1 in comparison to a previous study based on vanillin, giving, for the same figures of merit values, about 13 L g-1 and 0.2-0.3 mg L-1, respectively. The calibration curves for the standard solution and drugs were almost superimposable, therefore excluding interference from the excipients and additives, with very good reproducibility (avRSD% 2-4%) within the linear dynamic range (10 mg L-1-50 mg L-1).

Colorimetric determination of carbidopa in anti-Parkinson drugs based on 4-hydroxy-3-methoxybenzaldazine formation by reaction with vanillin.

In this paper is reported the selective colorimetric detection and quantification of carbidopa, an inhibitor of aromatic amino acid decarboxylase, in the co-presence of levodopa as dopamine precursor in pharmaceutical formulations for the treatment of Parkinson's disease. The method is based on the selective condensation reaction between the hydrazine group from carbidopa and the formyl functional group of vanillin, a natural flavoring agent, in acidified alcoholic solution. The yellow color development (λmax ~ 420 nm) due to the formation of 4-hydroxy-3-methoxybenzaldazine (HMOB) was observed for carbidopa only, whereas levodopa, lacking the hydrazine group, did not color the solution, as expected. The calibration curves for two tablet formulations of levodopa in combination with carbidopa (4:1) were superimposable with levodopa/carbidopa (4:1), as well as carbidopa alone, in standard solution, i.e., the excipients and additives did not interfere with carbidopa determination, corresponding to a mean recovery about 105%. The linear dynamic range was between 5.00 and 50.0 mg L-1 with very good reproducibility within this range (CVav% about 3-4%) and very good sensitivity, with limits of quantification of about 1 mg L-1. The colorimetric method developed here is very simple, inexpensive, and effective for drug estimation and quality control of pharmaceutical formulations.

Blue and green emission-transformed fluorescent copolymer: Specific detection of levodopa of anti-Parkinson drug in human serum.

Levodopa, commonly used anti-Parkinson drugs in the clinic, is the most significant prodrug of dopamine that plays important roles in the treatment of Parkinson's disease. Therefore, monitoring content of levodopa of anti-parkinson drugs in human serum is extremely necessary. Herein, a simple, fast and low-cost method for levodopa detection is proposed depending on the in situ formation of blue and green emission fluorescent copolymer (FCP). The proposed method is based on the conversion of fluorescence emission peak of FCP from blue (430 nm) to green emission (535 nm) in 2 h. In this sensing system, both blue and green emission exhibit a high selectivity and sensitivity for levodopa determination in the range from 0 to 50 µM with a detection limit of 0.2 µM and 0.36 µM, respectively. Among them green emission FCP shows excellent recovery even at human serum concentrations up to 30%. Additionally, the proposed method was successfully applied to assess the content of levodopa in three anti-Parkinson drugs (carbidopa and levodopa CR tablets, levodopa and benserazide hydrochloride tablets, and levodopa tablets). More importantly, the levodopa determination of three anti-Parkinson drugs in human serum also exhibit an excellent recovery. Therefore, our strategy provides a promising method for mechanism study and treatment of Parkinson's disease.

Efficient Electrochemical Sensor Based on Gold Nanoclusters/Carbon Ionic Liquid Crystal for Sensitive Determination of Neurotransmitters and Anti-Parkinson Drugs.

Purpose: Herein we introduce a simple and sensitive sensor for the electrochemical determination of neurotransmitters compounds and anti-Parkinson drugs. Methods: The electrochemical sensor (Au/CILCE) based on gold nanoclusters modified carbon ionic liquid crystal (ILC) electrode was characterized using scanning electron microscopy and voltammetry measurements. Results: The effect of ionic liquid type in the carbon paste composite for the electro-catalytic oxidation of L-dopa was evaluated. Highest current response was obtained in case of ILC compared to other studied kinds of ionic liquids. The effective combination of gold nanoclusters and ILC resulted in extra advantages including large surface area and high ionic conductivity of the nanocomposite. L-dopa is considered one of the most important prescribed medicines for treating Parkinson's disease. Moreover, a binary therapy using L-dopa and carbidopa proved effective and promising as it avoids the short comings of L-dopa mono-therapy for Parkinson's patients. The Au/CILCE can detect L-dopa in human serum in the linear concentration range of 0.1 µM to 90 µM with detection and quantification limits of 4.5 nM and 15.0 nM, respectively. Also, the Au/CILCE sensor can simultaneously and sensitively detect L-dopa in the presence of carbidopa with low detection limits. Conclusion: The sensor is advantageous to be applicable for electrochemical sensing of other biologically electroactive species.

Use of antidepressants in Parkinson's disease: A Swedish register-based study of over 1.5 million older people.

INTRODUCTION: It has been suggested that depression in Parkinson's Disease (PD) is often unrecognized and undertreated. However, few previous studies have studied the use of antidepressants in a large sample of both home-dwelling and institutionalized elderly persons with PD. We aimed to study the use of antidepressants in older persons using anti-parkinson drugs (APD, used as a proxy for PD), stratified by residential setting. METHODS: We analyzed individual data on age, sex, residential setting and drug use in over 1.5 million older persons in the Swedish Prescribed Drug Register on 31th of December 2013. RESULTS: Twenty-two percent of the home-dwellers and 50% of the institutionalized elderly persons with APD used antidepressants. Persons with APD had a higher probability of use of any antidepressant compared to persons without APD. A selective serotonin reuptake inhibitor (SSRI) was the most commonly used antidepressants in both settings followed by mirtazapin. CONCLUSIONS: The high use of antidepressants among older persons with APD warrants further studies on the quality of treatment of depression in PD.

Reasons driving treatment modification in Parkinson's disease: results from the cross-sectional phase of the REASON study.

OBJECTIVES: To assess the association between clinical and socio-demographic features and anti-Parkinson drug (APD) treatment modifications in patients with PD and to describe neurologist and patient opinions regarding the need for changes in APD therapy. METHODS: Subjects with PD with stable APD treatment over ≥3 months prior to baseline were enrolled and evaluated for socio-demographic data, disability, disease severity and neurologist and patient views on the need to modify APD treatment. RESULTS: 775 Patients were included, 51% with Hoehn and Yahr (HY) stage 1-2 (early PD) and 49% with HY stage 2.5-4 (advanced PD). Neurologists modified APD treatment in 255 patients, 97 (25%) early PD and 158 (41%; p < 0.0001) advanced PD. APD modification was strongly associated with a low educational level and UPDRS part IV score. The most common reasons behind the APD therapy changes among neurologists were presence/worsening of motor or non-motor symptoms (88% and 37% of subjects respectively). Out of 216 patients, 92% and 51% were willing to undergo APD changes to therapy because of the presence/worsening of motor or non-motor symptoms. CONCLUSIONS: Neurologist decision to change APD therapy and patients reasons for dissatisfaction with it can be prevalently attributed to the presence/worsening of motor symptoms and motor fluctuations in the advanced stages. Non-motor symptoms were considered more often by patients. The patient educational level played a key role in treatment decision.