Journal Cover
Drugs
Journal Prestige (SJR): 1.547
Citation Impact (citeScore): 5
Number of Followers: 200  
 
  Full-text available via subscription Subscription journal
ISSN (Print) 0012-6667 - ISSN (Online) 1179-1950
Published by Adis Homepage  [21 journals]
  • Lusutrombopag: A Review in Thrombocytopenia in Patients with Chronic Liver
           Disease Prior to a Scheduled Procedure
    • Abstract: Lusutrombopag (Mulpleta®), an orally bioavailable, small molecule thrombopoietin receptor agonist, is approved for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure. In placebo-controlled phase 3 clinical trials, lusutrombopag significantly increased the proportion of patients who did not require a platelet transfusion prior to the procedure or rescue therapy for bleeding up to 7 days after the scheduled procedure. Lusutrombopag also significantly increased the proportion of patients who were responders (i.e. had a platelet count ≥ 50 × 109/L and an increase of ≥ 20 × 109/L from baseline) compared with placebo. Lusutrombopag is well tolerated, with headache being the most common adverse reaction in lusutrombopag recipients in clinical trials. Thus, lusutrombopag represents a promising emerging therapeutic option for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure.
      PubDate: 2019-09-16
       
  • Correction to: Triamcinolone Acetonide Extended-Release: A Review in
           Osteoarthritis Pain of the Knee
    • Abstract: An Online First version of this article was made available online at https://rd.springer.com/article/10.1007/s40265-019-01083-3 on the 8th of March 2019. One error was identified in the article; please note the following
      PubDate: 2019-09-06
       
  • Trifluridine/Tipiracil: A Review in Metastatic Gastric Cancer
    • Abstract: Trifluridine/tipiracil (Lonsurf®) is a fixed-dose combination tablet comprising trifluridine, an antineoplastic nucleoside analogue, and tipiracil, a thymidine phosphorylase inhibitor. Trifluridine/tipiracil has recently been granted an additional indication in the USA for the treatment of metastatic gastric cancer, including gastroesophageal junction adenocarcinoma, in patients who have been previously treated with at least two systemic treatment regimens, and has received a positive opinion for this indication in the EU. In the large pivotal phase III TAGS trial, trifluridine/tipiracil plus best supportive care (BSC) significantly prolonged overall survival (OS; primary endpoint) compared with placebo plus BSC in this patient group. Progression-free survival (PFS) and the disease control rate were also improved with trifluridine/tipiracil relative to placebo. Health-related quality of life was not adversely affected by the addition of trifluridine/tipiracil to BSC and time to deterioration of Eastern Cooperative Oncology Group (ECOG) performance status was significantly delayed. The most common adverse events were mainly haematological (neutropenia, leucopenia and anaemia) and gastrointestinal (nausea, vomiting and diarrhoea), and were generally manageable with dosage modifications and/or supportive care. Adverse events ≥ Grade 3 were most frequently haematological in nature. Thus, trifluridine/tipiracil provides a valuable and much needed treatment option for patients with metastatic gastric or gastroesophageal junction adenocarcinoma that has progressed on at least two prior therapies.
      PubDate: 2019-09-06
       
  • Apalutamide: A Review in Non-Metastatic Castration-Resistant Prostate
           Cancer
    • Abstract: Apalutamide (marketed as Erleada®) is an oral non-steroidal next-generation selective inhibitor of the androgen receptor (AR), and is approved in several countries, including the USA and those of the EU, for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC). In men with nmCRPC who were receiving androgen-deprivation therapy (ADT) and had a high risk of metastases in SPARTAN, apalutamide significantly prolonged metastasis-free survival (MFS) compared with placebo, with consistent benefits demonstrated across subgroups. The addition of apalutamide to ongoing ADT significantly prolonged time to metastasis and progression-free survival (PFS) compared with placebo, and maintained health-related quality of life (HR-QOL). Apalutamide was generally well tolerated in SPARTAN, with fatigue being the most frequently reported adverse event. Given the available evidence, apalutamide with ongoing ADT represents an emerging treatment option for patients with nmCRPC who are at high risk of developing metastatic disease.
      PubDate: 2019-09-06
       
  • Targeting Granulocyte-Monocyte Colony-Stimulating Factor Signaling in
           Rheumatoid Arthritis: Future Prospects
    • Abstract: Rheumatoid arthritis (RA) is a systemic, autoimmune disease that affects joints and extra-articular structures. In the last decade, the management of this chronic disease has dramatically changed with the introduction of several targeted mechanisms of action, such as tumor necrosis factor-α inhibition, T-cell costimulation inhibition, B-cell depletion, interleukin-6 blockade, and Janus kinase inhibition. Beyond its well-known hematopoietic role on the proliferation and differentiation of myeloid cells, granulocyte-monocyte colony-stimulating factor (GM-CSF) is a proinflammatory mediator acting as a cytokine, with a proven pathogenetic role in autoimmune disorders such as RA. In vitro studies clearly demonstrated the effect of GM-CSF in the communication between resident tissue cells and activated macrophages at chronic inflammation sites, and confirmed the elevation of GM-CSF levels in inflamed synovial tissue of RA subjects compared with healthy controls. Moreover, a pivotal role of GM-CSF in the perception of pain has been clearly confirmed. Therefore, blockade of the GM-CSF pathway by monoclonal antibodies directed against the cytokine itself or its receptor has been investigated in refractory RA patients. Overall, the safety profile of GM-CSF inhibitors seems to be very favorable, with a particularly low incidence of infectious complications. The efficacy of this new mechanism of action is comparable with main competitors, even though the response rates reported in phase II randomized controlled trials (RCTs) appear to be numerically lower than the response rates observed with other biological disease-modifying antirheumatic drugs already licensed for RA. Mainly because of this reason, nowadays the development program of most GM-CSF blockers for RA has been discontinued, with the exception of otilimab, which is under evaluation in two phase III RCTs with a head-to head non-inferiority design against tofacitinib. These studies will likely be useful for better defining the potential role of GM-CSF inhibition in the therapeutic algorithm of RA. On the other hand, the potential role of GM-CSF blockade in the treatment of other rheumatic diseases is now under investigation. Phase II trials are ongoing with the aim of evaluating mavrilimumab for the treatment of giant cell arteritis, and namilumab for the treatment of spondyloarthritis. Moreover, GM-CSF inhibitors have been tested in osteoarthritis and diffuse subtype of systemic sclerosis. This review aims to describe in detail the available evidence on the GM-CSF blocking pathway in RA management, paving the way to a possible alternative treatment for RA patients. Novel insights regarding the potential use of GM-CSF blockers for alternative indications will be also addressed.
      PubDate: 2019-09-04
       
  • Janus Kinase Inhibition for Graft-Versus-Host Disease: Current Status and
           Future Prospects
    • Abstract: Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a curative treatment for many hematological malignant and non-malignant diseases. A major complication of the procedure is the donor T-cell-mediated graft-versus-host disease (GvHD). GvHD accounts for about 10% of early mortality after transplantation. GVHD is also the major cause of morbidity and disability in the late follow-up phase of transplanted patients, mainly because of the low response to first-line steroids, and the lack of efficient second-line standard treatments. The increasing knowledge regarding GVHD pathogenesis provides new pharmacological targets, potentially exploitable in clinical practice, in order to prevent and treat this complication. This review provides a description of GVHD pathogenesis, with a focus on the central role of the Janus kinase-related mechanisms. The first inflammatory innate-immunity response is triggered by a JAK/STAT dependent pathway, and JAK inhibition impairs antigen-presenting cell differentiation and activation and downregulates the expression of signals for T-cell triggering. The chronic evolution of alloreactivity, characterized by the long-term maintenance of inflammation and fibrosis, is also dependent on JAK/STAT activation. Based on preclinical data, we reviewed the rationale behind the clinical use of JAK-inhibitors in GVHD, presenting available results of clinical trials and reports, and looked at future implementation of this new promising treatment approach.
      PubDate: 2019-09-01
       
  • Prothrombin Complex Concentrates are Superior to Fresh Frozen Plasma for
           Emergency Reversal of Vitamin K Antagonists: A Meta-Analysis in 2606
           Subjects
    • Abstract: Background Urgent reversal of vitamin K antagonists (VKAs) is required for major bleeding or urgent surgery by intravenous vitamin K with either prothrombin complex concentrates (PCCs) or fresh frozen plasma (FFP). However, there is lack of consensus regarding the superiority of either reversal agent. We sought to compare the performance of PCC and FFP in urgent reversal of VKA. Methods A meta-analysis was conducted up to November 2018. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model. Results Seventeen studies comprising 2606 participants met the inclusion criteria. Compared with FFP treatment, PCC treatment led to a reduction in 90-day all-cause mortality (OR 0.60, 95% CI 0.40–0.90, p = 0.01), better reversal of INR (OR 7.36, 95% CI 4.18–12.98; p < 0.00001) and lower risk of at least one treatment-related adverse event (OR 0.45, 95% CI 0.26–0.80, p = 0.006). Among patients with VKA-associated intracranial haemorrhage, PCC treatment led to a reduction in 90-day all-cause mortality (OR 0.58, 95% CI 0.35–0.94, p = 0.03) and better reversal of INR (OR 6.52, 95% CI 1.66–25.59, p = 0.007). There were no differences between these two agents in thrombogenicity, requirement for and quantity of red blood cell transfusions, all adverse events, fluid overload or disability on discharge or at 90 days. Conclusions As an agent for urgent reversal of VKA, PCC outperforms FFP in 90-day all-cause mortality including those with VKA-related intracranial haemorrhage, INR reversal and treatment-related adverse events.
      PubDate: 2019-09-01
       
  • Prevention of Cisplatin-Induced Acute Kidney Injury: A Systematic Review
           and Meta-Analysis
    • Abstract: Purpose Cisplatin-induced acute kidney injury (CIA) is a serious adverse event that affects 20–40% of exposed patients, despite any implemented precaution to avoid it. The aim of this work was therefore to identify a relevant nephroprotective method for CIA. Methods We searched Pubmed, Embase, and Web of Science from 1 January 1978 to 1 June 2018, without language restriction. All studies (observational and interventional) assessing a CIA prevention method for adults receiving at least one course of cisplatin were eligible. The primary outcome was acute nephrotoxicity, as defined by the AKI-KDIGO classification (2012). The odds ratio and corresponding 95% confidence interval were used to assess the associations. We used narrative synthesis in case of heterogeneity regarding intervention, population, or outcome. When possible, a random-effects model was used to pool studies. The heterogeneity between studies was quantified (I2), and multiple meta-regressions were carried out to identify potential confounders. Results Within 4520 eligible studies, 51 articles fulfilling the selection criteria were included in the review, assessing 21 different prevention methods. A meta-analysis could only be performed on the 15 observational studies concerning magnesium supplementation (1841 patients), and showed a significant nephroprotective effect for all combined grades of CIA (OR 0.24, [0.19–0.32], I2 = 0.0%). This significant nephroprotective effect was also observed for grades 2 and 3 CIA (OR 0.22, [0.14–0.33], I2 = 0.0% and OR 0.25, [0.08–0.76], I2 = 0.0%, respectively). Conclusion While no method of prevention had so far demonstrated its indisputable efficacy, our results highlight the potential protective effect of magnesium supplementation on cisplatin-induced acute nephrotoxicity. Trial Registration This study is registered in PROSPERO, CRD42018090612.
      PubDate: 2019-09-01
       
  • Bremelanotide: First Approval
    • Abstract: Bremelanotide (Vyleesi™) is a melanocortin receptor agonist recently approved in the USA for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), as characterized by low sexual desire that causes marked distress or interpersonal difficulty. It is a self-administered, on-demand subcutaneous therapy. Initially developed by Palatin Technologies who sponsored the Phase 3 clinical trials, bremelanotide was subsequently out-licensed to AMAG Pharmaceuticals Inc. for exclusive North American rights to develop and commercialize the drug, including submitting the New Drug Application to the US FDA. Bremelanotide is a synthetic peptide analogue of the neuropeptide hormone alpha melanocyte-stimulating hormone (α-MSH) with high affinity for the melanocortin type 4 receptor (thought to be important for sexual function), giving it the potential to modulate brain pathways involved in sexual response. This article summarizes the milestones in the development of bremelanotide leading to this first regulatory approval.
      PubDate: 2019-09-01
       
  • The Evolving Biomarker Landscape for Treatment Selection in Metastatic
           Colorectal Cancer
    • Abstract: The approval of targeted therapies for metastatic colorectal cancer (mCRC) has led to important improvements in patient outcomes. However, it is still necessary to increase individualisation of treatments based on tumour genetic profiles to optimise efficacy, while minimising toxicity. As such, there is currently great focus on the discovery and validation of further biomarkers in mCRC, with many new potential prognostic and predictive markers being identified alongside developments in patient molecular profiling technologies. Here, we review data for validated and emerging biomarkers impacting treatment strategies in mCRC. We completed a structured literature search of the PubMed database to identify relevant publications, limiting for English-language publications published between 1 January 2014 and 11 July 2018. In addition, we performed a manual search of the key general oncology and CRC-focused congresses to identify abstracts reporting emerging mCRC biomarker data, and of ClinicalTrials.gov to identify ongoing clinical trials investigating emerging biomarkers in mCRC and/or molecular-guided clinical trials. There is solid evidence supporting the use of BRAF status as a prognostic biomarker and DYPD, UGT1A1, RAS, and microsatellite instability as predictive biomarkers in mCRC. There are a number of emerging biomarkers that may prove to be clinically relevant in the future to have prognostic (HPP1 methylation), predictive (HER3, microRNAs, anti-angiogenic markers, and CRC intrinsic subtypes), or both prognostic and predictive values (HER2, CpG island methylator phenotype, tumour mutational load, gene fusions, and consensus molecular subtypes). As such, new biomarker-led treatment strategies in addition to anti-epidermal growth factor receptor and anti-angiogenetic treatments are being explored. Biomarkers that are not recommended to be tested in clinical practice or are unlikely to be imminently clinically relevant for mCRC include thymidylate transferase, ERCC1, PIK3CA, and PTEN. We highlight the clinical utility of existing and emerging biomarkers in mCRC and provide recommended treatment strategies according to the biomarker status. An update on ongoing molecular-guided clinical trials is also provided.
      PubDate: 2019-09-01
       
  • Entrectinib: First Global Approval
    • Abstract: Entrectinib (Rozlytrek®) is an oral selective inhibitor of the tyrosine kinases tropomyosin receptor kinases (Trk)A/B/C [encoded by the genes neurotrophic tyrosine receptor kinase (NTRK) 1, 2 and 3, respectively], c-ros oncogene 1 (ROS1) and anaplastic lymphoma kinase (ALK) with central nervous system (CNS) activity developed by Roche for the treatment of various solid tumours harbouring NTRK1/2/3 or ROS1 gene fusions. In June 2019, entrectinib received its first global approval in Japan, for the treatment of adult and paediatric patients with NTRK fusion-positive, advanced or recurrent solid tumours and is under regulatory review for the treatment of adult patients with ROS1-positive non-small cell lung cancer (NSCLC). Entrectinib is also under regulatory review in the USA (PDUFA date 18 August 2019) and EU [Priority Medicines (PRIME) designation] for NTRK-positive solid tumours and ROS1-positive NSCLC. This article summarizes the milestones in the development of entrectinib leading to this first global approval for solid tumours in Japan.
      PubDate: 2019-09-01
       
  • Polatuzumab Vedotin: First Global Approval
    • Abstract: Polatuzumab vedotin (polatuzumab vedotin-piiq; Polivy™) is an antibody–drug conjugate comprising a monoclonal antibody against CD79b (a B cell receptor component) covalently conjugated to the anti-mitotic cytotoxic agent monomethyl auristatin (MMAE) via a cleavable linker. After binding to CD79b on the B-cell surface, polatuzumab vedotin is internalized and the linker is cleaved, releasing MMAE into the cell, where it inhibits division and induces apoptosis. Polatuzumab vedotin is being developed by Genentech (a subsidiary of Roche) for the treatment of haematological malignancies. In June 2019, the US FDA granted accelerated approval to polatuzumab vedotin, in combination with bendamustine plus rituximab, for the treatment of adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who have received at least two prior therapies. Use of the compound in combination with bendamustine plus rituximab is also under regulatory review for relapsed/refractory DLBCL in the EU and is in ongoing phase 1b/2 development in this setting or relapsed/refractory follicular lymphoma (FL) in several countries. Various other polatuzumab vedotin combination therapy regimens are also in phase 1b/2 development for relapsed/refractory non-Hodgkin lymphoma (NHL) [including DLBCL and FL] or in phase 2 or 3 development for previously untreated DLBCL, while polatuzumab vedotin monotherapy has been in phase 1 development for relapsed/refractory B-cell NHL in Japan. This article summarizes the milestones in the development of polatuzumab vedotin leading to this first approval for its use in combination with bendamustine plus rituximab for relapsed/refractory DLBCL.
      PubDate: 2019-09-01
       
  • Recent Clinical Advances in Pharmacotherapy for Levodopa-Induced
           Dyskinesia
    • Abstract: Onset of involuntary movement patterns of the face, body and limbs are known as dyskinesia. They mostly appear in association with long-term levodopa (l-dopa) therapy in patients with Parkinson’s disease. Consequences include patient distress, caregiver embarrassment and reduced quality of life. A severe intensity of this motor complication may result in troublesome disability; however, patients typically prefer motor behaviour with slight, non-troublesome dyskinesia to ‘OFF’ states. Pharmacotherapy of dyskinesia is complex. Continuous nigrostriatal postsynaptic dopaminergic receptor stimulation may delay onset of l-dopa-associated dyskinesia, while non-physiological, ‘pulsatile’ receptor stimulation facilitates appearance of dyskinesia. In the past, there have been many clinical trial failures with compounds that were effective in animal models of dyskinesia. Only the N-methyl-d-aspartate antagonist amantadine has shown moderate antidyskinetic effects in small well-designed clinical studies. Amantadine is an old antiviral compound, which moderately improves impaired motor behaviour. Recently, there has been a resurgence of its use due to the US Food and Drug Administration approval of an extended-release (ER) amantadine formulation for treatment of l-dopa-induced dyskinesia. This pharmacokinetic innovation improved dyskinesia and ‘OFF’ states in pivotal trials, with a once-daily oral application in the evening. Amantadine ER provides higher and more continuous amantadine plasma bioavailability than conventional immediate-release formulations, which require administration up to three times daily.
      PubDate: 2019-09-01
       
  • Take-Home Naloxone for the Emergency Interim Management of Opioid
           Overdose: The Public Health Application of an Emergency Medicine
    • Abstract: Naloxone is a well-established essential medicine for the treatment of life-threatening heroin/opioid overdose in emergency medicine. Over two decades, the concept of ‘take-home naloxone’ has evolved, comprising pre-provision of an emergency supply to laypersons likely to witness an opioid overdose (e.g. peers and family members of people who use opioids as well as non-medical personnel), with the recommendation to administer the naloxone to the overdose victim as interim care while awaiting an ambulance. There is an urgent need for more widespread naloxone access considering the growing problem of opioid overdose deaths, accounting for more than 100,000 deaths worldwide annually. Rises in mortality are particularly sharp in North America, where the ongoing prescription opioid problem is now overlaid with a rapid growth in overdose deaths from heroin and illicit fentanyl. Using opioids alone is dangerous, and the mortality risk is clustered at certain times and contexts, including on prison release and discharge from hospital and residential care. The provision of take-home naloxone has required the introduction of new legislation and new naloxone products. These include pre-filled syringes and auto-injectors and, crucially, new concentrated nasal sprays (four formulations recently approved in different countries) with speed of onset comparable to intramuscular naloxone and relative bioavailability of approximately 40–50%. Choosing the right naloxone dose in the fentanyl era is a matter of ongoing debate, but the safety margin of the approved nasal sprays is superior to improvised nasal kits. New legislation in different countries permits over-the-counter sales or other prescription-free methods of provision. However, access remains uneven with take-home naloxone still not provided in many countries and communities, and with ongoing barriers contributing to implementation inertia. Take-home naloxone is an important component of the response to the global overdose problem, but greater commitment to implementation will be essential, alongside improved affordable products, if a greater impact is to be achieved.
      PubDate: 2019-09-01
       
  • Glycopyrronium/Formoterol: A Review in COPD
    • Abstract: Glycopyrronium/formoterol (Bevespi Aerosphere®) is a fixed-dose combination of the long-acting muscarinic antagonist glycopyrronium bromide and the long-acting β2-agonist formoterol fumarate delivered via a pressurized metered dose inhaler (pMDI) and formulated using co-suspension delivery technology. It is approved in the USA and EU for use as maintenance treatment in patients with chronic obstructive pulmonary disease (COPD) and in Japan to relieve symptoms in patients with COPD. In the PINNACLE trials in patients with moderate to very severe COPD, glycopyrronium/formoterol was associated with significantly greater improvements in lung function than its monocomponents and placebo at 24 weeks and its monocomponents and open-label tiotropium over 52 weeks. In the AERISTO trial, glycopyrronium/formoterol was non-inferior to umeclidinium/vilanterol dry powder inhaler for peak change in forced expiratory volume in 1 s (FEV1) within 2 h postdose, but not for the change in morning predose trough FEV1, over 24 weeks. Glycopyrronium/formoterol was generally well tolerated in patients with moderate to very severe COPD, with most adverse events (AEs) being of mild or moderate severity. Thus, glycopyrronium/formoterol pMDI formulated using co-suspension delivery technology is a useful new addition that extends treatment options for patients with COPD.
      PubDate: 2019-08-29
       
  • Correction to: Camrelizumab: First Global Approval
    • Abstract: Page 1355, , Inline table ‘Camrelizumab (AiRuiKa™): Key Points’, and Introduction.
      PubDate: 2019-08-24
       
  • Correction to: Damoctocog Alfa Pegol: A Review in Haemophilia A
    • Abstract: The article Damoctocog Alfa Pegol: A Review in Haemophilia A, written by Julia Paik and Emma D. Deeks, was originally published Online First without open access.
      PubDate: 2019-08-23
       
  • Sacubitril/Valsartan: Updates and Clinical Evidence for a
           Disease-Modifying Approach
    • Abstract: New therapeutic strategies aimed to tackle the rising socio-economic burden of heart failure (HF) have become an impelling priority. The new pharmacological class of angiotensin (Ang) receptor-neprilysin inhibitors (ARNI) prompted a real conceptual change in the treatment of HF moving from only the inhibition of the renin-Ang-aldosterone system and sympathetic nervous system to a strategy based on the concomitant pharmacological enhancement of endogenous natriuretic peptides. Sacubitril/valsartan, a first-in-class ARNI, has reduced the primary composite endpoint of cardiovascular death or HF hospitalisation, sudden cardiac death, disease progression and improved quality of life, compared with enalapril, in patients on evidence-based contemporary medical therapy. Our review underlines the increasing body of evidence supporting the efficacy of sacubitril/valsartan, which may be considered a new disease-modifying therapy and, after about 30 years of research, a real step forward in HF pharmacological therapy.
      PubDate: 2019-08-20
       
  • Selinexor: First Global Approval
    • Abstract: Selinexor (XPOVIO™) is a first-in-class, oral, small molecule Exportin-1 (XPO1) inhibitor that is being developed by Karyopharm Therapeutics for the treatment of cancer. Selinexor (in combination with dexamethasone) received accelerated approval in the USA in July 2019 for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM). Selinexor is also undergoing clinical development in a wide range of haematological and solid cancers. This article summarizes the milestones in the development of selinexor leading to this first approval for RRMM.
      PubDate: 2019-08-19
       
  • Pharmacological and Therapeutic Properties of Cannabidiol for Epilepsy
    • Abstract: Cannabidiol (CBD) is a major active component of the Cannabis plant, which, unlike tetrahydrocannabinol (THC), is devoid of euphoria-inducing properties. During the last 10 years, there has been increasing interest in the use of CBD-enriched products for the treatment of epilepsy. In 2018, an oil-based highly purified liquid formulation of CBD (Epidiolex) derived from Cannabis sativa was approved by the US Food and Drug Administration for the treatment of seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). The mechanisms underlying the antiseizure effects of CBD are unclear but may involve, among others, antagonism of G protein-coupled receptor 55 (GPR55), desensitization of transient receptor potential of vanilloid type 1 (TRPV1) channels, and inhibition of adenosine reuptake. CBD has complex and variable pharmacokinetics, with a prominent first-pass effect and a low oral bioavailability that increases fourfold when CBD is taken with a high-fat/high-calorie meal. In four randomized, double-blind, parallel-group, adjunctive-therapy trials, CBD given at doses of 10 and 20 mg/kg/day administered in two divided administrations was found to be superior to placebo in reducing the frequency of drop seizures in patients with LGS and convulsive seizures in patients with DS. Preliminary results from a recently completed controlled trial indicate that efficacy also extends to the treatment of seizures associated with the tuberous sclerosis complex. The most common adverse events that differentiated CBD from placebo in controlled trials included somnolence/sedation, decreased appetite, increases in transaminases, and diarrhea, behavioral changes, skin rashes, fatigue, and sleep disturbances. About one-half of the patients included in the DS and LGS trials were receiving concomitant therapy with clobazam, and in these patients a CBD-induced increase in serum levels of the active metabolite norclobazam may have contributed to improved seizure outcomes and to precipitation of some adverse effects, particularly somnolence.
      PubDate: 2019-08-01
       
 
 
JournalTOCs
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Email: journaltocs@hw.ac.uk
Tel: +00 44 (0)131 4513762
Fax: +00 44 (0)131 4513327
 
Home (Search)
Subjects A-Z
Publishers A-Z
Customise
APIs
Your IP address: 18.206.194.83
 
About JournalTOCs
API
Help
News (blog, publications)
JournalTOCs on Twitter   JournalTOCs on Facebook

JournalTOCs © 2009-