Mikko Vahteristo

Treatment of restless legs syndrome

OBJETIVO: A sindrome das pernas inquietas e um transtorno neurologico caracterizado por um desejo incontrolavel de mover os membros, que comumente esta somente presente ou piora ao descanso ou a noite. O objetivo do trabalho foi a revisao da literatura disponivel sobre o tratamento farmacologico para a sindrome das pernas inquietas. METODO: Pesquisa da literatura recente realizada em bases de dados eletronicas (Medline, Pubmed, Scielo e Lilacs). RESULTADOS: Quinhentos e dois artigos foram encontrados, dos quais 30 foram selecionados. Os agentes dopaminergicos, os anticonvulsantes, os opioides, os benzodiazepinicos, o zolpidem, o entacapone e a ketamina foram eficazes no tratamento da sindrome das pernas inquietas. Um estudo mostrou que o ferro nao foi eficaz. CONCLUSOES: Baseado nos poucos estudos duplo-cegos, randomizados e controlados, parece que as melhores opcoes para tratar os pacientes com sindrome das pernas inquietas sao a gabapentina e L-dopa associada a sua formulacao de liberacao lenta.

Entacapone Prolongs the Reduction of PLM by Levodopa/Carbidopa in Restless Legs Syndrome

Objectives: Levodopa is effective in the treatment of restless legs syndrome (RLS). However, due to the short duration of action of conventional levodopa/decarboxylase inhibitor formulations, multiple dosing may be required in individual patients with persisting symptoms. We assessed whether a new levodopa formulation containing levodopa, carbidopa, and entacapone (LCE) improves levodopa action in RLS. Methods: Twenty-eight RLS patients with periodic limb movement (PLM) received single doses of Stalevo 50 (LCE50; 50/12.5/200 mg), Stalevo 100 (LCE100; 100/25/200 mg), Stalevo 150 (LCE150; 150/37.5/200 mg), Sinemet 100 (LC100; 100/25 mg), or placebo in a randomized, double-blind, crossover study with polysomnography. Periodic limb movements per hour (PLM/h) during total sleep time and PLM during total time in bed were the primary and secondary variables, respectively. Results: Mean PLM/h during total sleep time after Stalevo 50 (12.6/h, P < 0.05), LCE100, LCE150, and LC100 (6.4/h, 3.5/h and 9.5/h, respectively; P < 0.01) were significantly reduced compared with placebo (25.7/h). Improvement was also observed in PLM/h during total time in bed for all treatments (P < 0.01) and a significant dose response observed between LCE doses (P < 0.05). Compared with LC100, LCE100 and LCE150 reduced PLMs during the second half (P = 0.06 and P < 0.001, respectively) or during the last 3 early morning hours (hours 5-7 from the start of recording) of the night (P < 0.05 and P < 0.01, respectively). All formulations were well tolerated. Conclusions: Single doses of LCE tablets decreased PLMs in a dose-related manner in RLS patients. Prolonged effects of levodopa on PLMs suggest that, compared with standard levodopa, this new levodopa formulation provides longer symptom control throughout the night in patients with previously untreated RLS.

Pooled analysis of phase III with entacapone in Parkinson's disease

To investigate efficacy and safety of entacapone across phase III studies in Parkinsons disease (PD) with wearing‐off symptoms.

Clinically Equivalent Bronchodilatation Achieved with Formoterol Delivered via Easyhaler® and Aerolizer®

Background: User-friendly devices for the delivery of asthma drugs are needed to enhance treatment compliance. Formoterol inhalation powder has been developed to Easyhaler® multidose powder inhaler to enable the treatment of all asthma severities with the same device. Objectives: This double-blind, double-dummy, single- dose, placebo-controlled, cross-over study aimed to demonstrate the non-inferiority of the bronchodilating effect of formoterol 12 µg delivered via Easyhaler versus via Aerolizer®. In addition, dose responses following placebo, 12-µg and 48-µg doses of formoterol via Easyhaler were compared. Furthermore, onset and duration of action, and safety of formoterol inhaled using the two inhalers were compared. Methods: Sixty-seven adult asthmatic subjects showing ≧15% increase in forced expiratory volume in 1 s (FEV1) after short-acting sympathomimetic inhalation were enrolled and completed the study. The study comprised screening and 4 treatment days, with each subject inhaling a single 12-µg dose of formoterol via Easyhaler, a 12-µg dose via Aerolizer, a 48-µg dose via Easyhaler or placebo. Repeat spirometry and vital sign measurements were performed for 12 h during treatment days. The primary efficacy variable was the area under the flow volume curve (AUC0–12) of FEV1. Secondary efficacy variables comprised maximum FEV1 (FEV1max), forced vital capacity (FVC), and the need of rescue medication during the treatment days. Safety was evaluated by determining blood pressure, heart rate and the number of adverse events (AEs). Results: Results showed the non-inferiority of the bronchodilating effect of 12 µg formoterol via Easyhaler® compared to Aerolizer®. The Easyhaler-Aerolizer ratio for AUC0–12 of FEV1 was 0.991 (95% confidence interval from 0.969 to 1.013). No statistically significant differences emerged for secondary efficacy variables. A statistically significant dose response was seen following placebo, 12- and 48-µg doses in FEV1. No safety differences emerged for the 12-µg dose inhaled via Easyhaler or Aerolizer, but the incidence of AEs was higher following formoterol 48 µg and placebo treatments. Conclusions: Formoterol delivered via Easyhaler was therapeutically equivalent to Aerolizerat the 12-µg dose. The 48-µg dose via Easyhaler demonstrated statistically significantly greater bronchodilation but showed an increased occurrence of AEs.

Entacapone and Prostate Cancer Risk in Patients With Parkinson's Disease

The association between Parkinsons disease (PD) and prostate cancer, both common in elderly men, is disputable. In the STRIDE‐PD study, prostate cancer developed in 9 patients (3.7%) receiving levodopa/carbidopa with entacapone, a catechol‐O‐methyltransferase inhibitor, versus 2 cases (0.9%) without entacapone. The current pharmacoepidemiological study aimed to determine whether entacapone increases prostate cancer incidence or mortality in PD patients and whether cumulative exposure affects these rates.

In Vitro Flow Rate Dependency of Delivered Dose and Fine Particle Dose of Salmeterol/Fluticasone Propionate Easyhaler and Seretide Diskus with Patient Flow Rates Collected in a Randomized Controlled Trial

Abstract Background: The Easyhaler® device-metered dry powder inhaler containing Salmeterol and Fluticasone propionate (S/F) has been developed for the treatment of patients with asthma and chronic obstructive pulmonary disease (COPD). We report two studies which evaluated the in vitro flow rate dependence of delivered dose (DD) and fine particle dose (FPD) of S/F Easyhaler versus Seretide Diskus®. Methods: A randomized controlled trial (RCT) assessed inspiratory flow parameters of S/F Easyhaler and Seretide Diskus in subgroups of patients with asthma (children, adolescents and adults, and elderly) and in COPD patients. The 10th, 50th, and 90th percentile airflow rates were determined and utilized in vitro, to evaluate flow rate dependence of DD and FPD. Flow rate dependence was evaluated relative to the result obtained at the 50th percentile and any values deviating from 100% indicated flow rate dependence. The volumetric flow rate dependence (Q) index derived from FPD at 10th and 90th percentile airflows was also evaluated. Results: Overall, 227 patients were enrolled and randomized; 216 completed the RCT. In total, 55.5% of patients were female, and the mean age was 46.3 years. Clinically relevant airflow rates (46, 68, and 85 L/min for S/F Easyhaler and 44, 71, and 96 L/min for Seretide Diskus) were carried forward into the in vitro study, which demonstrated similar flow rate dependence of DD and FPD for S/F Easyhaler compared with Seretide Diskus; all values were within ±15% limits across the 10th, 50th, and 90th percentile airflow rates. Q index results suggested that both S/F Easyhaler and Seretide Diskus are medium airflow-dependent products. Conclusions: Similar in vitro flow rate dependence of DD and FPD was demonstrated for S/F Easyhaler compared with Seretide Diskus, across a range of clinically relevant airflow rates, collected from patients with asthma and COPD.