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Atomoxetine is a drug widely used for the treatment of the attention deficit hyperactivity disorder (ADHD) with reduced risk of adverse motor reactions and chemical dependence. However, the pharmacokinetics characteristics as well as the toxicological risk of atomoxetine deserves further investigation to comprehensively analyze the therapeutic and safety aspects of this drug. This study aimed to predict the physicochemical profile and medicinal chemistry characteristics of atomoxetine, alongside its pharmacokinetic properties-namely absorption, distribution, metabolism, and excretion-as well as its toxicology (ADMET) potential through the utilization of web-based in silico tools. This research emphasizes predicted physicochemical, medicinal chemistry, and absorption parameters of atomoxetine that could influence the efficacy and safety of this drug for ADHD treatment. Additionally, atomoxetine also presents noteworthy predicted risks of hepatotoxicity, cardiotoxicity, neurotoxicity, nephrotoxicity, respiratory system toxicity, skin toxicity, and carcinogenicity. These findings underscore the necessity for further assessments of atomoxetine's safety profile, particularly considering different patient populations and durations of drug treatment. The data reported here from in silico predictions suggest that closer monitoring is warranted when atomoxetine is administered to patients with ADHD. Moreover, controlled studies detailing reliable protocols for personalized dosing, considering the multifactorial variability in metabolism efficiency and toxicological potential, would enable a more comprehensive assessment of atomoxetine's safety profile.

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BACKGROUND: Based on previous in vivo studies and human trials, intrathecal cell delivery is a safe and relevant therapeutic tool for improving patient's quality of life with neurological conditions. We aimed to characterise the safety profile of intrathecally delivered Mesenchymal stem cells (MSCs). METHODS: Ovid MEDLINE, Embase, Scopus, Cochrane Library, KCI-Korean Journal Database, and Web of Science. Databases were searched from their inception until April 13, 2023. Randomised Controlled Trials (RCTs) that compared intrathecal delivery of MSCs to controls in adult populations were included. Adverse events (AEs) were pooled and meta-analysed using DerSimonian-Laird random effects models with a correction factor 0.5 added to studies with zero count cells. Pooled AEs were described using Risk ratio (RR) and 95% confidence intervals (95% CI). Then, a random-effects meta-regress model on study-level summary data was performed to explore the relationship between the occurrence of AEs and covariates thought to modify the overall effect estimate. Finally, publication bias was assessed. RESULTS: 303 records were reviewed, and nine RCTs met the inclusion criteria and were included in the quantitative synthesis (n = 540 patients). MSCs delivered intrathecally, as compared to controls, were associated with an increased probability of AEs of musculoskeletal and connective tissue disorders (categorised by Common Terminology Criteria for Adverse Events-CTCAE version 5.0) (RR: 1.61, 95% CI 1.19-2.19, I2 = 0%). The random-effects meta-regress model suggested that fresh MSCs increased the probability of occurrence of AEs compared to cryopreserved MSCs (RR: 1.554; p-value = 0.048; 95% CI 1.004-2.404), and the multiple-dose, decreased the probability of AEs by 36% compared to single doses (RR: 0.644; p-value = 0.048; 95% CI 0.416-0.996); however, univariate random effects meta-regression models revealed a not significant association between the occurrence of AEs from MSCs intrathecal delivery and each covariate. CONCLUSIONS: Intrathecal delivery of MSCs was associated with a slight increase in AEs associated with musculoskeletal and connective tissue disorders, albeit without serious AEs. We conclude that intrathecal MSCs delivery is safe for patients with neurological conditions. However, further high-quality, large-scale RCTs are needed to confirm these findings.

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The potentiation of pharmacological effects can be achieved through several strategies, such as the association of substances and delivery in nanostructured systems. In practice, potentiation can be measured by the law of mass action and joint evaluation of the combination index (CI) and dose-response curves. In this context, this study aimed to evaluate the anti-inflammatory effect of the association of ß-caryophyllene and indomethacin in the free form and delivered in nanoemulsions using the in vitro model of LPS-stimulated murine macrophage. The results indicated potentiation of the anti-inflammatory effect of nanoemulsified substances compared to free substances, as well as synergistic action between the sesquiterpene and the selected NSAID. In comparison, the association of ß-caryophyllene and indomethacin in the free form inhibited the production of nitric oxide by 50% at 48.60 µg/mL (CI = 0.21), while the nanoemulsified association of these substances resulted in an IC50 of 1.45 µg/mL (CI = 0.14). In parallel, cytotoxicity assays on HaCaT and MRC-5 cell lines demonstrated the safety of IC50-equivalent concentrations of the anti-inflammatory action, and no irritating effects on the chorioallantoic membrane of embryonated eggs were observed (HET-CAM assay). The results suggest that ß-caryophyllene may be an alternative to replace an inert oily core in nanoemulsion systems when anti-inflammatory effects are desirable.

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Although bivalirudin has been recently made available for purchase in China, large-scale analyses on the safety profile of bivalirudin among Chinese patients is lacking. Thus, this study aimed to compare the safety profile of bivalirudin and heparin as anticoagulants in Chinese ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). A total of 1063 STEMI patients undergoing PCI and receiving bivalirudin (n=424, bivalirudin group) or heparin (n=639, heparin group) as anticoagulants were retrospectively enrolled. The net adverse clinical events (NACEs) within 30 days after PCI were recorded, including major adverse cardiac and cerebral events (MACCEs) and bleeding events (bleeding academic research consortium (BARC) grades 2-5 (BARC 2-5)). The incidences of NACEs (10.1 vs 15.6%) (P=0.010), BARC 2-5 bleeding events (5.2 vs 10.3%) (P=0.003), and BARC grades 3-5 (BARC 3-5) bleeding events (2.1 vs 5.5%) (P=0.007) were lower in the bivalirudin group compared to the heparin group, whereas general MACCEs incidence (8.9 vs 6.4%) (P=0.131) and each category of MACCEs (all P>0.05) did not differ between two groups. Furthermore, the multivariate logistic analyses showed that bivalirudin (vs heparin) was independently correlated with lower risk of NACEs (OR=0.508, P=0.002), BARC 2-5 bleeding events (OR=0.403, P=0.001), and BARC 3-5 bleeding events (OR=0.452, P=0.042); other independent risk factors for NACEs, MACCEs, or BARC bleeding events included history of diabetes mellitus, emergency operation, multiple lesional vessels, stent length >33.0 mm, and higher CRUSADE score (all P<0.05). Thus, bivalirudin presented a better safety profile than heparin among Chinese STEMI patients undergoing PCI.

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Introducción: Los antinflamatorios no esteroideos son los medicamentos más recetados por reumatólogos y traumatólogos. Pero a pesar de tener una eficacia similar para controlar la inflamación y el dolor, los diferentes antinflamatorios no esteroideos disponibles presentan variabilidad en su perfil de seguridad. Objetivo: Brindar una panorámica sobre la prescripción de protectores gástricos en pacientes reumatológicos, en dos centros hospitalarios, desde una perspectiva gastroenterológica. Métodos: La investigación se inscribe en el paradigma cuantitativo con un estudio observacional. Se conformaron dos grupos de pacientes, uno de ellos provenientes del hospital A y el segundo grupo pertenecía al hospital B. Discusión: Los gastroprotectores se han convertido en los fármacos de mayor demanda en las farmacias comunitarias de Ecuador, y los más prescritos son los inhibidores de la bomba de protones y en menor frecuencia los antihistamínicos H2. Respecto a los gastroprotectores más frecuentemente prescritos, según nuestro estudio, estos valores podrían obedecer a la disponibilidad y los costos de la famotidina y el omeprazol con respecto a otros medicamentos de probada eficacia (ansoprazol, pantoprazol, rabeprazol y ranitidina). Conclusiones: Durante los últimos años, el uso de los fármacos gastroprotectores en América Latina ha experimentado un importante desarrollo, con la observancia de normas y guías clínicas de manejo de casos que ofrecen recomendaciones importantes al respecto. Por tanto, desde una perspectiva gastroenterológica, para tener éxito, es indispensable procurar un conocimiento de estos aportes y evidencias científicas(AU)

Introduction: Nonsteroidal anti-inflammatory drugs are the most prescribed medications by rheumatologists and traumatologists. However, despite having similar efficacy in controlling inflammation and pain, the different available nonsteroidal anti-inflammatory drugs show variability in their safety profile. Objective: To provide an overview of the prescription of gastric protectors in rheumatological patients, in two hospital centers, from a gastroenterological perspective. Methods: The research is part of the quantitative paradigm with an observational study. Two groups of patients were formed, one of them from hospital A and the second group belonged to hospital B. Discussion: Gastroprotectors have become the drugs in greatest demand in community pharmacies in Ecuador, the most prescribed being Proton Pump Inhibitors (IBPS) and, to a lesser extent, H2 antihistamines (anti-H2). Regarding the most frequently prescribed gastroprotectors, according to our study, these values ​​could be due to the availability and costs of famotidine and omeprazole compared to other drugs with proven effectiveness, such as ansoprazol, pantoprazole, rabeprazole and ranitidine. Conclusions: In recent years, the use of gastroprotective drugs in Latin America has undergone significant development, with the observance of clinical case management norms and guidelines that offer important recommendations in this regard. Therefore, from a gastroenterological perspective, to be successful, it is essential to seek knowledge of these contributions and scientific evidence(AU)

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Randia ferox is a Brazilian native species used in folk medicine. Scientific information regarding the toxicology and phytochemistry of this plant remains unclear. We aimed to produce a R. ferox extract, identify its chemical matrix, and evaluate its safety profile. The extract chemical composition was accessed through UHPLC-MS/MS. Mononuclear cells, erythrocytes, fibroblasts, macrophages, and kidney cells were subjected to extract concentration-response curve testing. The cellular viability, proliferation, dsDNA release, reactive oxygen species (ROS), nitric oxide (NO), hemolysis, and DNA damage were determined. Ten molecules were found in the extract matrix. Most of the tested concentrations can be considered safe. Cellular viability, proliferation, dsDNA release, and NO remained at similar levels to the control. The extract increased ROS in macrophages. None of the tested concentrations induced DNA damage or hemolysis. The data suggest R. ferox extract contains several bioactive molecules and has a safety profile in vitro.

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Aim: To enhance the tretinoin (TRE) safety profile through the encapsulation in nanostructured lipid carriers (NLC). Materials & methods: NLC-TRE was developed using a 23 experimental factorial design, characterized (HPLC, dynamic light scattering, differential scanning calorimetry, x-ray diffraction analysis, transmission electron microscopy, cryo-transmission electron microscopy) and evaluated by in vitro studies and in healthy volunteers. Results: The NLC-TRE presented spherical structures, average particle size of 130 nm, zeta potential of 24 mV and encapsulation efficiency of 98%. The NLC-TRE protected TRE against oxidation (p < 0.0001) and promoted epidermal targeting (p < 0.0001) compared with the marketed product, both 0.05% TRE. The in vitro assay on reconstructed human epidermis and the measurement of transepidermal water loss in healthy volunteers demonstrated an enhanced safety profile in comparison to the marketed product (p < 0.0002). Conclusion: The NLC-TRE enhances the epidermal targeting and safety profile of TRE, representing a potential safer alternative for the topical treatment of skin disorders using TRE.

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The development of an effective vaccine against SARSCoV-2 has turned into a global priority in order to stop the advance of this ongoing COVID-19 pandemic. To date there are 25 candidate vaccines currently in a clinical trial stage, 3 of which have been subjected to phase I/II preliminary reports (ChAdOx1 nCoV-19, BNT162b1 and mRNA-1273). These vaccines have demonstrated to elicit robust cellular and humoral immune responses when compared to convalescent patients serum samples and have shown an acceptable safety profile with no reported severe side effects. Here we discuss the reported evidence regarding these vaccines.

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OBJECTIVES: To summarize the procedure for reporting adverse drug reactions (ADRs) in a Mexican hospital, with the purpose of promoting and facilitating the report of ADRs by the heath team. We outline the relevance of pharmacists in performing these activities in Mexican hospitals. METHODS: A pharmacovigilance study was carried out following the establishment of the Pharmacovigilance Unit of a Mexican hospital on January 2014 through March 2019. KEY FINDINGS: There is an undernotification rate of ADRs, since only 137 ADRs were notified in a five-year period, mostly by biopharmaceutical chemists holding bachelor's degrees that were acting as pharmacists. CONCLUSIONS: To improve the safety of medications, it is necessary to improve ADR notifications in Mexico's health system. One important step in this direction is to establish a Pharmacy degree with training for promoting and performing ADR notifications.

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INTRODUCCIÓN: La enfermedad tromboembólica venosa está comprendida por la trombosis venosa profunda y el tromboembolismo pulmonar, las cuales son enfermedades comunes con alta morbilidad y mortalidad, incluso antes del diagnóstico. El tratamiento está basado principalmente en la terapia anticoagulante, con diferentes opciones dependiendo del ámbito clínico y la estabilidad del paciente (terapia oral vs parenteral). Objetivo: Revisar las diferentes opciones y escenarios clínicos para la indicación de terapia anticoagulante, basados en la evidencia médica actual. Metodología: Se realizó una búsqueda sistemática en las bases de datos PubMed, Scopus, Google Académico y Scielo sobre estudios que evaluaran la indicación de la terapia anticoagulante en pacientes con diagnóstico de enfermedad tromboembólica venosa, principalmente, estudios aleatorizados controlados y metaanálisis. Discusión y Resultados: Fueron encontrados estudios aleatorizados controlados donde se evidencian menores tasas de sangrado y recurrencia de la enfermedad tromboembólica venosa a favor de los anticoagulantes directos, excluyendo algunas situaciones especiales como cáncer y enfermedad renal crónica avanzada. Conclusión: La terapia anticoagulante es el pilar del tratamiento en la enfermedad tromboembólica, disminuyendo la morbilidad y mortalidad de esta entidad, aunque aumenta el riesgo de sangrado. Anteriormente, los anticoagulantes antagonistas de la vitamina K eran la única opción terapéutica, pero con altas tasas de sangrado, afortunadamente desde hace algunos años contamos con los anticoagulantes directos con mejores perfiles de seguridad y menor tasa de sangrado.

ABSTRACTS: Venous thromboembolic disease includes deep venous thrombosis and pulmonary embolism, which are common diseases with high morbidity and mortality. The treatment is based mainly on anticoagulant therapy, with different options depending on clinic context and patient stability (oral vs parenteral therapy). Objective: To review evidence based medical information regarding the use of anticoagulant therapy in venous thromboembolism. Methods: We performed a systematic review of PubMed, Scopus, Google scholar and Scielo databases, of randomized controlled studies and meta-analysis evaluating anticoagulant therapy in patients with thromboembolic venous disease. Results: Except for tromboembolic disease in patients with cancer or chronic kidney disease anticoagulation with direct (new) oral agents led to less bleeding episodes and lower relapse rate. Conclusion: anticoagulant therapy is the basis of treatment for thromboembolic disease, decreasing morbidity and mortality. New oral anticoagulants' are associated to better clinical results, notwithstanding a slight increase in bleeding episodes.

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Los estudios clínicos realizados antes de la comercialización del producto farmacéutico y la Farmacovigilancia contribuyen al diseño del perfil de seguridad de un medicamento y a detectar posibles riesgos en la población consumidora, es por ello que en la actualidad autoridades regulatorias a nivel mundial exigen la presentación de Planes de Manejo de Riesgos de Medicamentos como requisito para su registro. El objetivo de esta investigación fue proponer lineamientos que puedan definir el cumplimiento de estos planes y el rol de la autoridad regulatoria para el seguimiento de los mismos, dicha propuesta estuvo enmarcada como un proyecto mixto, documental y factible. Se realizó un análisis comparativo de diferentes países que permitió detectar oportunidades de mejora sobre este tópico en Venezuela; con la finalidad de identificar aspectos importantes para realizar la propuesta de lineamientos, que será en pro de salvaguardar la salud de la población venezolana.

The clinical trials performed before of the commercialization of pharmaceuticals products and the Pharmacovigilance contribute to design of the safety profile of a medication and to detect possible risks in the consumer population, which is why today worldwide Regulatory Authorities require the submission of The Risk Management Plans of the medications as a requirement for registration. The objective of this research was to propose guidelines that can define the fulfillment of these plans and the role of the Regulatory Authority to monitor them, the proposal was framed as a mixed project, documentary and feasible. Was performed a comparative analysis of different countries which allowed to identify opportunities for improvement on this topic in Venezuela; in order to identify important aspects to the proposed guidelines, which will be in favor to safeguard the health of the Venezuelan population.

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