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Background: Different studies, mostly with limited cohorts, have suggested the effects of patients’ characteristics on levodopa (LD) pharmacokinetics. Objective: We primarily aimed at investigating in a large population the relationship between patients’ features and LD kinetic variables, to assess the main demographic and clinical predictors of LD clinical pharmacokinetics. Methods: The study was retrospective, based on data collected from subjects with parkinsonism on chronic LD undergoing LD therapeutic monitoring (TM). LD TM includes serial quantitative motor tests and blood samples to measure plasma drug concentrations after each subject’s chronically taken first-morning LD dose intake. Results: Five hundred patients, 308 males (61.6%), mean (SD) age of 65 (10.1) years were included. Parkinsonian symptoms and LD therapy lasted 5.5 (4.5) and 3.4 (3.9) years, respectively. MDS-UPDRS part III “off” score was 28.8 (15.2). LD dose was 348.2 (187.1) mg/day. From multiple linear regression analysis, test dose, sex, type of LD decarboxylase inhibitor, weight and MDS-UPDRS part III score were linear predictors of both LD peak plasma concentration (Cmax) (R2 = 0.52) and area under the 3-h plasma concentration-time curve (AUC) (R2 = 0.71), while age was a further predictor only for AUC. Besides test dose, sex was the strongest independent contributing variable to LD AUC, which resulted 27% higher in females compared to males. Conclusion: This is the largest collection of data on the relationship between demographic and clinical-therapeutic variables and LD kinetics in patients with parkinsonian symptoms. As a main clinically practical finding, women might require a 25% reduced weight-normalized LD dose compared with men to achieve the same LD bioavailability.

Raw data pertaining to the article "Cannabis-based products in a neurological setting: a clinical and pharmacokinetic survey" Authors:Susan Mohamed, Giovanna Lopane, Loredana Sabattini, Cinzia Scandellari, Diletta Zardi, Vincenzo Donadio, Giovanni Rizzo, Alessandro Perrone, Alessandra Lugaresi, Manuela Contin Abstract Background and aim: Limited data are available in clinical settings on the pharmacokinetics of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). We investigated the use of cannabis-based products in neurological practice, monitoring patients’ steady-state cannabinoids plasma concentrations matched with different preparations. Methods: This was a prospective, single-center, observational study. Patients underwent venous blood withdrawal before the cannabinoids’ morning dose, and then 2.5 hours post dosing. Spasticity or pain were patient self-assessed by the Numeric Rating Scale (NRS) before the morning cannabinoids administration and 2.5 hours post dosing. Results: Thirty-three patients were enrolled. Main indications for cannabinoids were spasticity and chronic pain. Sixteen patients were treated with oromucosal spray formulation and 17 with oil-based solutions. Both cannabinoids’ trough plasma concentrations were ≤ limit of detection (0.1 ng/ml) in 45% of patients. Intrasubject cannabinoids’ plasma levels significantly increased over baseline values in patients treated with Bediol® oil (p Conclusion: This is the first study investigating cannabinoids plasma concentrations of oral and oromucosal preparations in real-world neurological practice. Findings of similar bioavailability for both CBD and THC after galenic oil compared with oromucosal spray dosing may be clinically relevant and deserve additional research in larger cohorts. &nbsp

This paper describes the second part of the PASSO (Parkinson smart sensory cues for older users) project, which designs and tests an innovative haptic biofeedback system based on a wireless body sensor network using a smartphone and different smartwatches specifically designed to rehabilitate postural disturbances in persons with Parkinson’s disease. According to the scientific literature on the use of smart devices to transmit sensory cues, vibrotactile feedback (particularly on the trunk) seems promising for improving people’s gait and posture performance; they have been used in different environments and are well accepted by users. In the PASSO project, we designed and developed a wearable device and a related system to transmit vibrations to a person’s body to improve posture and combat impairments like Pisa syndrome and camptocormia. Specifically, this paper describes the methodologies and strategies used to design, develop, and test wearable prototypes and the mHealth system. The results allowed a multidisciplinary comparison among the solutions, which led to prototypes with a high degree of usability, wearability, accessibility, and effectiveness. This mHealth system is now being used in pilot trials with subjects with Parkinson’s disease to verify its feasibility among patients.

Introduction: Pramipexole (PRA), ropinirole (ROP) and rotigotine (ROT) are non-ergoline dopaminergic agonists (DAs) used to treat Parkinson's disease (PD). Clinical pharmacokinetics of DAs is poorly characterized in PD. The main purpose of our study was to investigate the effect of dose, age and sex on steady-state plasma concentrations of DAs in real life PD patients on chronic DAs therapy. Methods: The study was single center, open and prospective. Blood samples for measurement of DAs plasma concentrations were drawn in the morning, at a median 18-h distance from the last DA dose. Results: Ninety-one patients treated with PRA, 50 with ROP and 37 with ROT were enrolled in the study. Plasma concentration of DAs significantly correlated with weight-adjusted daily dose in all subgroups, although at a given dose, matched plasma concentrations highly varied among patients. Median PRA plasma concentration-to-daily dose ratio (C/D) [(ng/mL)/(mg/kg/d)] was 68% higher in patients >65 years than ≤65 years (158 vs 94, p < 0.001), while was not affected by age in ROP and ROT subgroups. No sex-mediated differences in C/D ratios were observed in any group. Conclusion: These are the first observations on DAs pharmacokinetics in PD patients’ everyday clinical practice. Of relevance, patients over 65yrs may require about one third of PRA dose compared to under 65yrs to achieve the same plasma concentration. Due to the high intersubject variability in plasma concentrations at the same dosage, we speculate that monitoring of plasma DAs might be helpful in the individualization of treatment in selected patients.

As an alternative to the technical industrial mindset, User-Centered Design has proven to be an effective tool to realize products and services for the Healthcare sector. In this scenario, this project aims to develop an innovative wearable gait rehabilitation solution obtained by integrating the Smart Glasses Vuzix Blade into the smartphone-based CuPiD-system. The specific aims of the testing phase described in this paper were to observe how submitted visual, auditory, and vibratory cues influence the user’s gait; and which were the most impacting and efficient typologies of cues. To achieve these results, we analyze the users’ qualitative and quantitative feedback, respectively obtained from an interview and a specific gait analysis protocol.

The differential diagnosis between multiple system atrophy with predominant parkinsonism (MSA-P) and Parkinson's disease (PD) may be challenging at disease onset. Levodopa responsiveness helps distinguish the two groups, but studies evaluating this issue using objective standardized tests are scanty. We retrospectively examined the extent of levodopa response by an objective kinetic-dynamic test in a series of patients prospectively followed up for a parkinsonian syndrome and eventually diagnosed as MSA-P or PD. Sixteen MSA-P and 31 PD patients under chronic levodopa therapy received a first morning fasting dose of levodopa/benserazide (100/25 mg) or levodopa/carbidopa (125/12.5 or 100/25 mg) and underwent simultaneous serial assessments of plasma levodopa concentration and alternate finger tapping frequency up to 3 h post dosing. The main levodopa pharmacodynamic variables were the maximum percentage increase in tapping frequency over baseline values (ΔTapmax %) and the area under the tapping effect-time curve (AUCTap). Levodopa pharmacokinetics did not show significant differences between MSA-P and PD, whereas both the magnitude and overall extent of levodopa tapping effect were markedly reduced in the MSA-P group (p < 0.001). The combined use of specific cut-off values for both the main pharmacodynamic variables, ΔTapmax %

Objectives: We compared levodopa (LD) kinetic-dynamic profile of a dose of LD/aromatic amino acid decarboxylase peripheral inhibitors versus a nominally equivalent dose of a commercial Mucuna pruriens (Mucuna) seeds extract in 2 patients with Parkinson disease chronically taking LD standard combined with self-prescribed Mucuna. Methods: Patients were challenged with a fasting morning dose of 100 mg LD/25 mg carbidopa (patient 1) or benserazide (patient 2) versus 100 mg LD from Mucuna capsules in 2 different sessions, after a 12-hour standard LD formulations’ washout. They underwent kinetic-dynamic LD monitoring based on LD dose intake and simultaneous serial assessments of plasma drug concentrations and motor test performances. Quantitative analysis of LD in Mucuna capsules was also performed. Results: Levodopa bioavailability was markedly lower after Mucuna administration compared with LD standard formulations: in patient 1, peak plasma LD concentration (Cmax) decreased from 2.0 to 1.0 mg/L and the area under the plasma concentration time curve from 137 to 33.6 mg/L per minute; in patient 2, Cmax was 0.7 mg/L after LD/benserazide and nearly undetectable afterMucuna. In patient 1, impaired LD bioavailability from Mucuna resulted in reduced duration and overall extent of drug response compared with LD/carbidopa. In patient 2, no significant subacute LD motor response was observed in either condition. Quantitative analysis of Mucuna formulation confirmed the 100 mg LD content for the utilized capsules. Conclusions: Our results show an impaired LD bioavailability from Mucuna preparation, as expected by the lacking aromatic amino acid decarboxylase inhibitors coadministration,whichmight explain the suggested lower dyskinetic potential of Mucuna compared with standard LD formulations.