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https://www.readbyqxmd.com/read/28335772/production-of-s-2-aminobutyric-acid-and-s-2-aminobutanol-in-saccharomyces-cerevisiae
#1
Nora Weber, Anaëlle Hatsch, Ludivine Labagnere, Harald Heider
BACKGROUND: Saccharomyces cerevisiae (baker's yeast) has great potential as a whole-cell biocatalyst for multistep synthesis of various organic molecules. To date, however, few examples exist in the literature of the successful biosynthetic production of chemical compounds, in yeast, that do not exist in nature. Considering that more than 30% of all drugs on the market are purely chemical compounds, often produced by harsh synthetic chemistry or with very low yields, novel and environmentally sound production routes are highly desirable...
March 23, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28331468/will-brivaracetam-help-my-patient-only-time-will-tell
#2
Jacqueline French
No abstract text is available yet for this article.
January 2017: Epilepsy Currents
https://www.readbyqxmd.com/read/28293101/new-developments-in-the-management-of-partial-onset-epilepsy-role-of-brivaracetam
#3
REVIEW
Giangennaro Coppola, Giulia Iapadre, Francesca Felicia Operto, Alberto Verrotti
Currently, a number of novel anticonvulsant drugs, the so-called third generation, are in various stages of development. Several of them are already available or in ongoing clinical trials. These new compounds should take advantage of new insights into the basic pathophysiology of epileptogenesis, drug metabolism and drug interactions. Many of them still need to be further evaluated mainly in real-world observational trials and registries. Among newer anticonvulsant drugs for partial-onset seizures (POSs), rufinamide, lacosamide, eslicarbazepine and perampanel are those new treatment options for which more substantial clinical evidence is currently available, both in adults and, to some extent, in children...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28280887/brivaracetam-population-pharmacokinetics-in-children-with-epilepsy-aged-1%C3%A2-month-to-16%C3%A2-years
#4
Rik Schoemaker, Janet R Wade, Armel Stockis
PURPOSE: The aims of the study were to develop a population pharmacokinetic model of orally administered brivaracetam in paediatric patients and to provide dosing suggestions. METHODS: Analysis included 600 brivaracetam plasma concentrations from a phase 2a study (NCT00422422; N01263) in 96 paediatric patients with epilepsy aged 1 month to 16 years, taking one to three concomitant antiepileptic drugs (AEDs). Pharmacokinetic analysis was performed using non-linear mixed effects modelling, and a stepwise covariate search was used to determine factors influencing brivaracetam clearance...
March 9, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28279891/efficacy-and-tolerability-of-adjunctive-brivaracetam-in-patients-with-prior-antiepileptic-drug-exposure-a-post-hoc-study
#5
Ali A Asadi-Pooya, Michael R Sperling, Steve Chung, Pavel Klein, Anyzeila Diaz, Sami Elmoufti, Jimmy Schiemann, John Whitesides
Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle protein 2A, is a new antiepileptic drug (AED) for adjunctive treatment of focal (partial-onset) seizures in adults with epilepsy. This post-hoc analysis was conducted to explore the efficacy of adjunctive BRV in patients with prior levetiracetam (LEV) exposure and whether changes in efficacy were related to the similar mechanism of action of these two drugs. Data were pooled from three Phase III studies (NCT00490035; NCT00464269; NCT01261325) of adults with focal seizures taking 1-2 AEDs who received placebo or BRV 50-200mg/day without titration over a 12-week treatment period...
February 27, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28236727/health-related-quality-of-life-in-double-blind-phase-iii-studies-of-brivaracetam-as-adjunctive-therapy-of-focal-seizures-a-pooled-post-hoc-analysis
#6
Christian Brandt, Simon Borghs, Sami Elmoufti, Knut Mueller, Rebecca Townsend, Christine de la Loge
PURPOSE: The effect of adjunctive brivaracetam on health-related quality of life (HRQoL) was assessed in a post-hoc analysis using pooled data from three randomized, double-blind, placebo-controlled Phase III studies in patients with refractory focal seizures (NCT00490035, NCT00464269, and NCT01261325). METHODS: The Patient-Weighted Quality of Life in Epilepsy Questionnaire (QOLIE-31-P) was completed at randomization, and weeks 4, 8 (in two of three studies), and 12 (end of the treatment period)...
February 22, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28220535/interaction-of-approved-drugs-with-synaptic-vesicle-protein-2a
#7
Azeem Danish, Vigneshwaran Namasivayam, Anke C Schiedel, Christa E Müller
Levetiracetam (LEV) and its recently approved derivative brivaracetam are anti-epileptic drugs with a unique mechanism of action. The synaptic vesicle protein 2A (SV2A) was previously identified as their main target. In the current study, we tested a collection of 500 approved drugs for interaction with the human SV2A protein expressed in Chinese hamster ovary cells. Competition binding studies were performed using cell lysates with high SV2A expression and [(3) H]brivaracetam as a radioligand. A hit rate of 3% was obtained, defined as compounds that inhibited radioligand binding by more than 90% at a screening concentration of 20 μM...
February 21, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28163554/brivaracetam-briviact-a-novel-adjunctive-therapy-for-partial-onset-seizures
#8
Farbod Khaleghi, Eric C Nemec
Brivaracetam (Briviact): a novel adjunctive therapy for partial-onset seizures.
February 2017: P & T: a Peer-reviewed Journal for Formulary Management
https://www.readbyqxmd.com/read/28111749/progress-report-on-new-antiepileptic-drugs-a-summary-of-the-thirteenth-eilat-conference-on-new-antiepileptic-drugs-and-devices-eilat-xiii
#9
REVIEW
Meir Bialer, Svein I Johannessen, René H Levy, Emilio Perucca, Torbjörn Tomson, H Steve White
The Thirteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIII) took place in Madrid, Spain, on June 26-29, 2016, and was attended by >200 delegates from 31 countries. The present Progress Report provides an update on experimental and clinical results for drugs presented at the Conference. Compounds for which summary data are presented include an AED approved in 2016 (brivaracetam), 12 drugs in phase I-III clinical development (adenosine, allopregnanolone, bumetanide, cannabidiol, cannabidivarin, 2-deoxy-d-glucose, everolimus, fenfluramine, huperzine A, minocycline, SAGE-217, and valnoctamide) and 6 compounds or classes of compounds for which only preclinical data are available (bumetanide derivatives, sec-butylpropylacetamide, FV-082, 1OP-2198, NAX 810-2, and SAGE-689)...
January 23, 2017: Epilepsia
https://www.readbyqxmd.com/read/28101765/tolerability-and-safety-of-commonly-used-antiepileptic-drugs-in-adolescents-and-adults-a-clinician-s-overview
#10
REVIEW
Martin J Brodie
This paper discusses the issues surrounding the tolerability and safety of the commonly used antiepileptic drugs (AEDs) in adolescents and adults. The content includes dose-related adverse effects, idiosyncratic reactions, behavioural and psychiatric comorbidities, chronic problems, enzyme induction and teratogenesis. Twenty-one AEDs are discussed in chronological order of their introduction into the UK, starting with phenobarbital and ending with brivaracetam. Wherever possible, advice is given on anticipating, recognising and managing these issues and thereby improving the lives of people with epilepsy, most of whom will need to take one or more of these agents for life...
January 18, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28012162/evidence-for-a-differential-interaction-of-brivaracetam-and-levetiracetam-with-the-synaptic-vesicle-2a-protein
#11
Martyn D Wood, Michel Gillard
OBJECTIVE: Brivaracetam (BRV) and levetiracetam (LEV) are effective antiepileptic drugs that bind selectively to the synaptic vesicle 2A (SV2A) protein. However, BRV differs from LEV in that it exhibits more potent and complete seizure suppression in animal models including in amygdala-kindled mice, where BRV afforded nearly complete seizure suppression. This raises the possibility that aside from potency differences, BRV and LEV may interact differently with the SV2A protein, which is not apparent in radioligand-binding competition studies...
February 2017: Epilepsia
https://www.readbyqxmd.com/read/28004320/sensitivity-and-responsiveness-of-the-eq-5d-3l-in-patients-with-uncontrolled-focal-seizures-an-analysis-of-phase-iii-trials-of-adjunctive-brivaracetam
#12
Clara Mukuria, Tracey Young, Anju Keetharuth, Simon Borghs, John Brazier
PURPOSE: Preference-based measures are required to measure the impact of interventions for cost-effectiveness analysis. This study assessed the psychometric performance of the EQ-5D-3L in adults with uncontrolled focal (partial-onset) seizures. METHODS: Data from three Phase III studies of an antiepileptic drug (adjunctive brivaracetam; n = 1095) were used. Analysis included correlations between EQ-5D-3L and Quality of Life in Epilepsy Inventory (QOLIE-31P) and seizure frequency...
March 2017: Quality of Life Research
https://www.readbyqxmd.com/read/27988967/time-to-onset-of-sustained-%C3%A2-50-responder-status-in-patients-with-focal-partial-onset-seizures-in-three-phase-iii-studies-of-adjunctive-brivaracetam-treatment
#13
Pavel Klein, Martin E Johnson, Jimmy Schiemann, John Whitesides
Time to onset of sustained ≥50% responder status (SRS) was assessed for the pooled patient population receiving brivaracetam (BRV) 50, 100, or 200 mg/day or placebo in three randomized phase III studies (NCT00464269, NCT00490035, and NCT01261325). Patients were aged ≥16 years with well-characterized focal (partial-onset) seizures (FS) uncontrolled by 1-2 concomitant antiepileptic drugs. After an 8-week baseline period, patients received study drug without up-titration for a 12-week (84-day) treatment period...
December 18, 2016: Epilepsia
https://www.readbyqxmd.com/read/27970520/cost-effectiveness-of-brivaracetam-versus-other-antiepileptic-drugs-used-as-adjunctive-treatment-for-focal-seizures-in-the-uk-a-discrete-event-simulation-model
#14
M Charokopou, J Sander, R Saha, S Beard, R Kidd, E Coward, J Plumb
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27970485/applying-the-accepted-techniques-of-indirect-treatment-comparison-to-meet-payer-needs-for-brivaracetam-versus-adjunctive-antiepileptic-medications-for-the-treatment-of-focal-seizures-in-adult-patients-do-they-reflect-the-need-for-individualised-patient-care
#15
M Charokopou, R Harvey, K Sristava, R Townsend, S Borghs
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27898363/the-adverse-event-profile-of-brivaracetam-a-meta-analysis-of-randomized-controlled-trials
#16
Li-Na Zhu, Deng Chen, Tao Chen, Da Xu, Si-Han Chen, Ling Liu
PURPOSE: To comprehensively evaluate the adverse events (AEs) significantly associated with brivaracetam (BRV) treatment in a large selection of randomized control trials. METHODS: We conducted an online database search using Pubmed, Embase, Cochrane Online Library, and Clinicaltrial.gov for all available randomized control trials (RCTs) that investigated the therapeutic effects of brivaracetam. Serious AEs (SAEs), withdrawal, and treatment-emergent adverse effects were then assessed for their association with brivaracetam...
February 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/27818243/impact-of-sodium-chloride-on-the-expansion-of-a-liquid-liquid-miscibility-gap-in-an-api-water-system-case-study-of-brivaracetam
#17
Nicolas Couvrat, Julien Mahieux, Baptiste Fours, Yohann Cartigny, Eric Schenkel, Luc Aerts, Luc Quéré, Gérard Coquerel
Brivaracetam, or (2S)-2-[(4R)-2-oxo-4-propyl-pyrrolidin-1-yl] butanamide, is an active pharmaceutical ingredient designed for the treatment of epilepsy. During the development of the IV administration mode, a liquid-liquid miscibility gap has been observed with pure water, isotonic and hypertonic solutions (vehicle at 0.9% w/w and 5%w/w NaCl respectively). The study reveals that the NaCl concentration has a direct impact on the extent of the demixing domain; from a sub-micronic demixing in pure water towards a macroscopic miscibility gap in hypertonic aqueous solutions...
December 30, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27800023/brivaracetam-as-adjunctive-therapy-for-the-treatment-of-partial-onset-seizures-in-patients-with-epilepsy-the-current-evidence-base
#18
REVIEW
Christian Brandt, Theodor W May, Christian G Bien
Brivaracetam (BRV) is a novel antiepileptic drug recently licensed for the treatment of partial epilepsy in adults and adolescents over 16 years old. Like levetiracetam (LEV), it is a ligand of the synaptic vesicle protein SV2A. BRV has been shown in animal models and in studies using human brain slices to have a higher SV2A affinity and faster penetration into the brain. Its efficacy and safety have been shown in several randomized, controlled studies. The recommended initial dose is 50-100 mg, divided into two daily doses...
November 2016: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/27768878/a-new-sv2a-ligand-for-epilepsy
#19
Michael A Rogawski
Since the 1970s, racetams have been in use as cognitive enhancers. Levetiracetam was discovered to have antiseizure activity in animal models and was then found to bind to SV2A in synaptic and endocrine vesicles. Brivaracetam, an analog of levetiracetam, was identified in a medicinal chemistry campaign with the objective of discovering analogs with higher affinity at racetam-binding sites and greater antiseizure potency.
October 20, 2016: Cell
https://www.readbyqxmd.com/read/27710868/efficacy-and-tolerability-of-brivaracetam-compared-to-lacosamide-eslicarbazepine-acetate-and-perampanel-as-adjunctive-treatments-in-uncontrolled-focal-epilepsy-results-of-an-indirect-comparison-meta-analysis-of-rcts
#20
REVIEW
Francesco Brigo, Nicola Luigi Bragazzi, Raffaele Nardone, Eugen Trinka
BACKGROUND: Brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM), and perampanel (PER) have been recently marketed as adjunctive treatments for focal onset seizures. To date, no randomized controlled trial (RCT) has directly compared BRV with ESL, LCM, or PER. PURPOSE: To compare BRV with the other add-on AEDs in patients with uncontrolled focal epilepsy, estimating their efficacy and tolerability through an adjusted, common-reference based indirect comparison meta-analysis...
November 2016: Seizure: the Journal of the British Epilepsy Association
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