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This e-book provides an overview of current technologies used to increase the topical/transdermal delivery of drugs, its protocols, advantages and limitations. It includes exclusive chapters on chemical enhancers, Iontophoresis, Sonophoresis, Electroporation, Microneedles and the more recent use of micro/nanoparticles to deliver drugs throughout the skin.

IntroductionSince 2011, the Spanish Society of Family Medicine has recommended general practitioners (GPs) to ask their patients to stop taking antibiotics when they suspect a viral infection. However, this practice is seldom used because uncertainty about diagnosis, and fear of consequences of discontinuing antibiotic therapy, as well as perceived pressure to continue prescribing antibiotics and potential conflict with patients are more of a concern for GPs than antibiotic resistance. The main objective of this study is to determine whether discontinuation of antibiotic therapy when a GP no longer considers it necessary has any impact on the number of days with severe symptoms.Methods and analysisThis is a multicentre, open-label, randomised controlled clinical trial. The study was conducted in 10 primary care centres in Spain. We included patients from 18 to 75 years of age with uncomplicated acute respiratory tract infections—acute rhinosinusitis, acute sore throat, influenza or acute bronchitis—who had previously taken any dose of antibiotic for <3 days, which physicians no longer considered necessary. The patients were randomly assigned to the usual strategy of continuing antibiotic treatment or to discontinuing antibiotic therapy. A sample size of 240 patients per group was calculated on the basis of a reduction of 1 day in the duration of severe symptoms being a clinically relevant outcome. The primary outcome was the duration of severe symptoms, that is, symptoms scored 5 or 6 by means of validated symptom diaries. Secondary outcomes included antibiotics taken, adverse events, patient satisfaction and complications within the first 3 months.Ethics and disseminationThe study was approved by the Ethical Board of Fundació Jordi Gol i Gurina (reference number: 16/093). The findings of this trial will bedisseminated through research conferences and peer-reviewed journals.Trial registration numberNCT02900820; pre-results.

The eye presents extensive perspectives and challenges for drug delivery, mainly because of the extraordinary capacity, intrinsic to this path, for drugs to permeate into the main circulatory system and also for the restrictions of the ocular barriers. Depending on the target segment of the eye, anterior or posterior, the specifications are different. The ocular route experienced in the last decades a lot of progresses related with the development of new drugs, improved formulations, specific-designed delivery and even new routes to administer a drug. Concomitantly, new categories of materials were developed and adapted to encapsulate drugs. With such advances, a multiplicity of parameters became possible to be optimized as the increase in bioavailability and decreased toxic effects of medicines. Also, the formulations were capable to easily adhere to specific tissues, increase the duration of the therapeutic effect and even target the delivery of the treatment. The ascending of new delivery systems for ocular targeting is a current focus, mainly because of the capacity to extend the normal time during which the drug exerts its therapeutic effect and, so, supplying the patients with a product which gives them fewer side effects, fewer number of applications and even more effective outcomes to their pathologies, surpassing the traditionally-used eye drops. Depending on the systems, some are capable of increasing the duration of the drug action as gels, emulsions, prodrugs, liposomes, and ocular inserts with hydrophilic properties, improving the absorption by the cornea. In parallel, other devices use as a strategy the capacity to sustain the release of the carried drugs by means of erodible and non-erodible matrices. This review discusses the different types of advanced formulations used for ocular delivery of therapeutics presenting the most recent patents according to the clinical applications.

Background Dose reduction schedules of tumor necrosis factor antagonists (anti-TNF) as maintenance therapy in patients with spondyloarthritis are used empirically in clinical practice, despite the lack of clinical trials providing evidence for this practice. Methods/Design To address this issue the Spanish Society of Rheumatology (SER) and Spanish Society of Clinical Pharmacology (SEFC) designed a 3-year multicenter, randomized, open-label, controlled clinical trial (2 years for inclusion and 1 year of follow-up). The study is expected to include 190 patients with axial spondyloarthritis on stable maintenance treatment (≥4 months) with any anti-TNF agent at doses recommended in the summary of product characteristics. Patients will be randomized to either a dose reduction arm or maintenance of the dosing regimen as per the official labelling recommendations. Randomization will be stratified according to the anti-TNF agent received before study inclusion. Patient follow-up, visit schedule, and examinations will be maintained as per normal clinical practice recommendations according to SER guidelines. The study aims to test the hypothesis of noninferiority of the dose reduction strategy compared with standard treatment. The first patients were recruited in July 2012, and study completion is scheduled for the end of April 2015. Discussion The REDES-TNF study is a pragmatic clinical trial that aims to provide evidence to support a medical decision now made empirically. The study results may help inform clinical decisions relevant to both patients and healthcare decision makers. Trial registration EudraCT 2011-005871-18 (21 December 2011)

This new book serves as an essential reference guide for planning and implementing a medication safety program. Provides a comprehensive analysis of principles and practices associated with the prevention and identification of medication errors.

Ivermectin is a pivotal drug for the control of onchocerciasis and lymphatic filariasis, which is increasingly identified as a useful drug for the control of other Neglected Tropical Diseases. Its role in the treatment of soil transmitted helminthiasis through improved efficacy against Trichuris trichiura in combination with other anthelmintics might accelerate the progress towards breaking transmission. Ivermectin is a derivative of Avermectin B1, and consists of an 80:20 mixture of the equipotent homologous 22,23 dehydro B1a and B1b. Pharmacokinetic characteristics and safety profile of ivermectin allow to explore innovative uses to further expand its utilization through mass drug administration campaigns to improve coverage rates. We conducted a phase I clinical trial with 54 healthy adult volunteers who sequentially received 2 experimental treatments using a new 18 mg ivermectin tablet in a fixed-dose strategy of 18 and 36 mg single dose regimens, compared to the standard, weight based 150–200 μg/kg, regimen. Volunteers were recruited in 3 groups based on body weight. Plasma concentrations of ivermectin were measured through HPLC up to 168 hours post treatment. Safety data showed no significant differences between groups and no serious adverse events: headache was the most frequent adverse event in all treatment groups, none of them severe. Pharmacokinetic parameters showed a half-life between 81 and 91 h in the different treatment groups. When comparing the systemic bioavailability (AUC0t and Cmax) of the reference product (WA-ref) with the other two study groups using fixed doses, we observed an overall increase in AUC0t and Cmax for the two experimental treatments of 18 mg and 36 mg. Body mass index (BMI) and weight were associated with t1/2 and V/F, probably reflecting the high liposolubility of IVM with longer retention times proportional to the presence of more adipose tissue. Systemic exposure to ivermectin (AUC0t or Cmax) was not associated with BMI or weight in our study. These findings contribute to further understand the pharmacokinetic characteristics of ivermectin, highlighting its safety across different dosing regimens. They also correlate with known pharmacokinetic parameters showing stable levels of AUC and Cmax across a wide range of body weights, which justifies the strategy of fix dosing from a pharmacokinetic perspective. ClinicalTrials.gov NCT03173742.

Historically, antimalarial drugs have been used at a population level in malaria-endemic areas with the objective of decreasing the burden, impact, and transmissibility of malaria.1 Continuous chemoprophylaxis, once experimented but never seriously considered a feasible wide-scale implementable strategy, has been superseded by the concept of intermittent treatment targeting different population groups, presenting many advantages, including non-interference with the acquisition of natural immunity against malaria.

In the wake of publicity and congressional attention to drug safety issues, the Food and Drug Administration (FDA) requested the Institute of Medicine assess the drug safety system. The committee reported that a lack of clear regulatory authority, chronic underfunding, organizational problems, and a scarcity of post-approval data about drugs' risks and benefits have hampered the FDA's ability to evaluate and address the safety of prescription drugs after they have reached the market. Noting that resources and therefore efforts to monitor medications' risk-benefit profiles taper off after approval, The Future of Drug Safety offers a broad set of recommendations to ensure that consideration of safety extends from before product approval through the entire time the product is marketed and used.

Ivermectin is a pivotal drug for the control of onchocerciasis and lymphatic filariasis, which is increasingly identified as a useful drug for the control of other Neglected Tropical Diseases. Its role in the treatment of soil transmitted helminthiasis through improved efficacy against Trichuris trichiura in combination with other anthelmintics might accelerate the progress towards breaking transmission. Ivermectin is a derivative of Avermectin B1, and consists of an 80:20 mixture of the equipotent homologous 22,23 dehydro B1a and B1b. Pharmacokinetic characteristics and safety profile of ivermectin allow to explore innovative uses to further expand its utilization through mass drug administration campaigns to improve coverage rates. We conducted a phase I clinical trial with 54 healthy adult volunteers who sequentially received 2 experimental treatments using a new 18 mg ivermectin tablet in a fixed-dose strategy of 18 and 36 mg single dose regimens, compared to the standard, weight based 150-200 μg/kg, regimen. Volunteers were recruited in 3 groups based on body weight. Plasma concentrations of ivermectin were measured through HPLC up to 168 hours post treatment. Safety data showed no significant differences between groups and no serious adverse events: headache was the most frequent adverse event in all treatment groups, none of them severe. Pharmacokinetic parameters showed a half-life between 81 and 91 h in the different treatment groups. When comparing the systemic bioavailability (AUC0t and Cmax) of the reference product (WA-ref) with the other two study groups using fixed doses, we observed an overall increase in AUC0t and Cmax for the two experimental treatments of 18 mg and 36 mg. Body mass index (BMI) and weight were associated with t1/2 and V/F, probably reflecting the high liposolubility of IVM with longer retention times proportional to the presence of more adipose tissue. Systemic exposure to ivermectin (AUC0t or Cmax) was not associated with BMI or weight in our study. These findings contribute to further understand the pharmacokinetic characteristics of ivermectin, highlighting its safety across different dosing regimens. They also correlate with known pharmacokinetic parameters showing stable levels of AUC and Cmax across a wide range of body weights, which justifies the strategy of fix dosing from a pharmacokinetic perspective.

A preformulation study of an oral lyophilisate with cetirizine dihydrochloride (CTZ) as active ingredient, mannitol and PVP K30 as bulking agents is presented. CTZ shown a humidity content of 0.150% and a spontaneous hygroscopicity of 0.200% (both determined by SeDeM diagram), demonstrating an adequate stability behavior in solid form. A design of experiments (DoE) performed with both mannitol and PVP K30, followed by a simple factorial design (32) has determined the optimum combination of excipients and CTZ, and showed that a higher proportion of PVP K30 was able to prevent metastable forms generated by mannitol.