Profile Of Drug Research Articles

In Vitro Drug Release and Ex Vivo Dermal Drug Permeation Studies of Selected Commercial Benzoyl Peroxide Topical Formulations: Correlation Between Human and Porcine Skin Models.

In vitro release testing (IVRT) serves as a crucial tool to assess the quality, physicochemical behavior, and performance of semisolid formulations already available on the market. In vitro skin permeation studies (IVPT) are widely used to evaluate the safety and efficacy profiles of topical drugs, utilizing biological membranes prepared from ex vivo human and porcine skin tissues. This study aimed to develop and validate a discriminative IVRT method to evaluate various marketed topical benzoyl peroxide formulations. Additionally, IVPT was employed to assess skin permeation and retention profiles of these formulations, comparing porcine skin results with those obtained by using ex vivo human skin tissues. Physicochemical differences among the evaluated benzoyl peroxide formulations were identified, with the poloxamer-based formulation exhibiting a higher release rate. IVPT using both porcine and human skin differentiated retention and skin permeation profiles, with the poloxamer-based formulation demonstrating greater skin retention capacity compared to the other formulations evaluated. Similar conclusions on benzoyl peroxide retention and cutaneous permeation were drawn from both porcine and human skin IVPT tests, confirming the correlation between the two models.

Research on genetic variant characteristics in ADME genes based on whole-exome sequencing in the Han Chinese population.

Genetic variants in absorption, distribution, metabolism, and excretion (ADME) genes affect drug efficacy and side effects. Whole-exome sequencing (WES) effectively identifies these variants. Findings from Western populations may not apply to the Han Chinese population due to ethnic differences. This study aimed to investigate genetic variants, metabolic phenotypes, and drug impacts related to ADME genes in the Han Chinese population using WES data. ADME genes and drug profiles were sourced from multiple databases. WES data were collected from 357 samples at Third Xiangya Hospital and 5,000 samples from the "HuaBiao Project." After WES, fastp was used for quality control; BWA, samtools, and the Picard software were used for comparison, sequencing, and de-duplication; GATK was used for base quality score recalibration; and variant quality score recalibration was carried out after detecting the variants, and the variants were annotated using ANNOVAR. ADME genes and drug profiles were obtained through PharmGKB and other databases, and then all variants in the exonic regions of ADME genes were extracted. The distributional characteristics of these variants, ethnic differences, and metabolic phenotype distribution of important ADME genes, such as CYP2B6, were analyzed. Prediction of deleterious variants of ADME gene employed the ADME gene variant prediction framework, and western blotting and enzyme assays were used to validate the impact of harmful variants. We integrated 604 ADME genes and 972 drugs. There were 33,925 single nucleotide polymorphisms (SNPs) and 484 insertion-deletions (InDels) in 5,357 Han Chinese WES samples; 88.9 % were rare. Of the SNPs, 60.9 % are new functional mutations in enzyme and transporter genes; InDels also affected these genes. We discovered Chinese-specific variants in key ADME genes and ethnic-specific metabolic phenotypes that could affect drug use. Finally, we screened 3,657 potentially harmful mutations; 45.6 % are novel. Western blotting and enzyme activity assays confirmed several harmful mutations significantly reduced CYP2C19 gene expression and function (P < 0.01).

Homoharringtonine in Relapsed/Refractory Paediatric T-Cell Acute Lymphoblastic Leukaemia-A Case Series and a Report on the Use of In Vitro Drug Profiling.

Paediatric relapse/refractory T-cell acute lymphoblastic leukaemia (T-ALL) is notoriously difficult to treat. This group of heavily pre-treated patients needs effective agents that can rapidly control the disease while not having significant toxicity. Homoharringtonine (HHT) has been widely used in children with acute myeloid leukaemia, but there is little information on T-ALL. In this case series, HHT, in combination with other agents, achieved good response in five paediatric patients with T-ALL. The in vitro drug profiling in one patient demonstrated clinical correlation with HHT activity. The study sheds light on the potential of precision medicine for patients with relapsed/refractory leukaemia.

Intravitreal Administration of Adalimumab‐Loaded Poly(Lactic‐co‐Glycolic Acid) Nanoparticles: Effects on Biodistribution and Pharmacokinetics

Adalimumab, a monoclonal antibody used for treating inflammatory diseases, including eye diseases, faces challenges in biodistribution and targeted delivery. Nanoparticle (NP)‐based drug delivery systems have shown promise in enhancing the pharmacokinetic profiles of biologic drugs. This study aims to develop, and characterize intravitreal adalimumab‐loaded poly(lactic‐co‐glycolic acid) (PLGA) NPs to improve antibody distribution and therapeutic efficacy. Characterization studies, morphological examination, and quantitative, stability, and physical properties are conducted. In vitro release kinetics are assessed using a dialysis membrane method. In vivo biodistribution is studied in rats after intravitreal administration by Positron Emission Tomography/Computed Tomography imaging. The optimized NPs were spherical (around 300 nm) with a surface charge of about −20 mV. Encapsulation efficiency and drug loading reach values close to 100%. Stability studies showed minimal changes in particle size and drug content. In vitro release showed a biphasic pattern with an initial burst release followed by sustained release. Safety studies indicated no significant cytotoxicity or adverse effects. The adalimumab‐loaded PLGA NPs demonstrate favorable physicochemical characteristics, stability, and release profiles. In vivo distribution revealed a change in the antibody's distribution pattern after intravitreal administration via NPs encapsulation. These findings suggest the potential for enhanced therapeutic outcomes and warrant further investigation in disease‐specific models to explore the clinical potential of this NP‐based delivery system.

New therapies in celiac disease.

Celiac disease (CeD) is a chronic autoimmune disorder of the small intestine triggered by gluten ingestion in genetically predisposed individuals. The cornerstone of CeD management remains a strict adherence to a lifelong gluten-free diet (GFD), although such a dietary restriction can lead to an altered quality of life and may not be easy to follow for many patients. These challenges highlighted the need for alternative therapies. This review aims to explore the latest advancements in these therapeutic avenues, emphasizing mechanisms of action, clinical efficacy, and safety profiles of drugs currently in advanced stages of clinical testing. Recent advances in the understanding of CeD pathophysiology have catalyzed the development of new therapeutic approaches, which include strategies to modify gluten processing in the gut, block gluten-triggered immune responses, or restore immune tolerance to gluten. While these therapies are not poised to take the place of GFD, they represent promising treatment alternatives that could enhance the quality of life and minimize long-term consequences in CeD patients. Further research, as well as phase III clinical trials of those already conducted, are needed to establish the feasibility of integrating these novel drugs in the clinical management of CeD.

Thermal Characterisation and Toxicity Profile of Potential Drugs from a Class of Disubstituted Heterofused Triazinones

The thermal characterisation and toxicity profile of a class of disubstituted heterofused triazinones were revealed in this article for the first time. The thermal behaviour of molecules 1–12 was investigated by means of TG and DSC analyses performed in an air atmosphere and by the coupled TG/FTIR technique in a nitrogen atmosphere. The heating atmosphere affects both the stability of compounds and the degradation mechanism. A two-step degradation occurs in air, while a one-step degradation takes place in nitrogen, both preceded by a melting process. Compound 3 shows the highest thermal stability, while molecule 10—the lowest. The thermal decomposition of the studied heterocyclic molecules begins with the degradation of the bicyclic system, resulting in the formation of volatile gaseous products such as ammonia/hydrazine, hydrogen cyanide, carbon dioxide, and isocyanates. In the further stage, mainly aromatic compounds are released, and their chemical composition depends on the presence and type of substituents at the phenyl and benzyl moieties. In addition, the toxicity profiles of molecules were assessed in the animal (zebrafish) and cellular (erythrocytes) models, and the antihaemolytic activity was evaluated in the AAPH- and H2O2-induced haemolysis inhibition assays. It was found that all the tested compounds are safe for the developing zebrafish and red blood cells, and they are able to effectively protect erythrocytes from oxidative damage. These favourable properties make them promising drug candidates suitable for further in vivo studies.

Prospective Utilization of Nanocarriers Loaded with Drug Combination for Treating Alzheimer's Disease.

Alzheimer's disease (AD) is a debilitating condition that significantly affects the elderly. Early diagnosis is not only critical for improving patient outcomes but also directly influences the success of emerging therapeutic interventions. A therapeutic strategy targeting only one pathogenic mechanism is unlikely to be very effective, as there is increasing evidence that AD does not have a single pathogenic cause. Therefore, combining medications or developing therapies that address multiple pathways may be beneficial. Most clinical trials can be classified under added therapy rather than combination therapy. Effective treatment of AD likely requires targeting multiple mechanisms, such as amyloid-beta (Aβ) and tau pathology. However, many medications face challenges, including poor solubility, low permeability, and the inability to cross the blood- -brain barrier (BBB). This is where nanocarriers come into play, as they can be loaded with these medications to facilitate targeted drug delivery. This approach enhances the pharmacokinetic profile of drugs in both the blood and the brain. Therefore, this paper provides a concise overview of the use of various nanocarriers loaded with drug combinations for treating AD.

Treatment of Seizures in People with Intellectual Disability.

There is a synergistic relationship between epilepsy and intellectual disability (ID), and the approach to managing people with these conditions needs to be holistic. Epilepsy is the main co-morbidity associated with ID, and clinical presentation tends to be complex, associated with higher rates of treatment resistance, multi-morbidity and premature mortality. Despite this relationship, there is limited level 1 evidence to inform treatment choice for this vulnerable population. This review updates the current evidence base for anti-seizure medication (ASM) prescribing for people with ID. Recommendations are made on the basis of evidence and expert clinical opinion and summarised into a Traffic Light System for accessibility. This review builds on work developed through UK's Royal College of Psychiatrists, Faculty of Intellectual Disability Psychiatry and includes newer pragmatic data from the Cornwall UK Ep-ID Research Register, a national research register for England and Wales that has been in existence for the last 10 years. The Register acts as a source for an in-depth exploration of the evidence base for prescribing 'newer' (third generation, specifically post-2004) ASMs. Its findings are discussed and compared. A practical approach to prescribing and choosing ASMs is recommended on the based evidence. This approach considers the drug profile, including adverse effects and clinical characteristics. The review also details newer specialist ASMs restricted to certain epilepsy syndromes, and potential future ASMs that may be available soon. For completeness, we also explore non-pharmacological interventions, including surgeries, to support epilepsy management.

Profile of drugs used by university students for self-medication in times of the COVID-19 pandemic: A scoping review

Profile of drugs used by university students for self-medication in times of the COVID-19 pandemic: A scoping review

Emerging Phytochemical Formulations for Management of Rheumatoid Arthritis: A Review.

Rheumatoid arthritis (RA) is a T-cell-mediated chronic inflammatory disorder affecting 0.5-1% of the global population. The disease with unknown etiology causes slow destruction of joints, advancing to significant deterioration of an individual's quality of life. The present treatment strategy comprises the use of disease-modifying anti-rheumatic drugs (DMARDs) coupled with or without nonsteroidal anti-inflammatory drugs or glucocorticoids. Additionally, involves co-therapy of injectable biological DMARDs in case of persistent or recurrent arthritis. The availability of biological DMARDs and the implementation of the treat-to-target approach have significantly improved the outcomes for patients suffering from RA. Nevertheless, RA requires continuous attention due to inadequate response of patients, development of tolerance and severe side effects associated with long-term use of available treatment regimens. An estimated 60-90% of patients use alternative methods of treatment, such as herbal therapies, for the management of RA symptoms. Over the past few decades, researchers have exploring natural phytochemicals to alleviate RA and associated symptoms. Enormous plant-origin phytochemicals such as alkaloids, flavonoids, steroids, terpenoids and polyphenols have shown anti-inflammatory and immunomodulatory activity against RA. However, phytochemicals have certain limitations, such as high molecular weight, poor water solubility, poor permeability, poor stability and extensive first-pass metabolism, limiting absorption and bioavailability. The use of nanotechnology has aided to extensively improve the pharmacokinetic profile and stability of encapsulated drugs. The current review provides detailed information on the therapeutic potential of phytochemicals. Furthermore, the review focuses on developed phytochemical formulations for RA, with emphasis on clinical trials, regulatory aspects, present challenges, and future prospects.

Assessing the benefit-risk profile of newer glucose-lowering drugs: A systematic review and network meta-analysis of randomized outcome trials.

To comprehensively evaluate the benefits and risks of glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase 4 inhibitors (DPP4i), and sodium-glucose cotransporter 2 inhibitors (SGLT2i). A systematic search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to November 2023 to identify randomized cardiovascular and kidney outcome trials that enrolled adults with type 2 diabetes, heart failure, or chronic kidney disease and compared DPP4i, GLP-1RAs, or SGLT2i to placebo. Twenty-one outcomes (e.g., major adverse cardiovascular events [MACE], stroke, and hospitalization for heart failure [HHF]) were assessed. Data were pooled using population-averaged odds ratios (ORs) with 95% CIs. Twenty-six trials enrolling 198 177 participants were included. GLP-1RAs were most effective in lowering the risks of MACE (OR, 0.85, [95% CI, 0.79 to 0.92]) and stroke (0.84 [0.77, 0.91]), but increased the risk of thyroid cancer (1.58 [1.36, 2.50]). SGLT2i showed the greatest benefits in reducing the risk of HHF (0.68 [0.64, 0.73]) and improving composite renal outcomes (0.67 [0.58, 0.77]), but increased the risk of genital infections (3.11 [2.15, 4.50]). DPP4i were associated with a lower risk of certain psychiatric disorders, Parkinson's disease (0.54 [0.32, 0.92]), and amputation (0.70 [0.86, 0.93]), but an increased risk of neuropathy (1.10 [1.02, 1.18]) and pancreatitis (1.63 [1.40, 1.91]). The weighted origami plot suggested that GLP-1RAs were more suitable for reducing macrovascular and microvascular outcomes, while DPP4i might be better for neurodegenerative diseases and cancer concerns. Given the distinct benefit-risk profiles, the selection of glucose-lowering drugs should be individualized based on patient characteristics and risk factors.

Evaluation of Practice and Awareness of the Safety Profile of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) among Dental Practitioners: A Cross-Sectional Study

Non-steroidal anti-inflammatory drugs (NSAIDs) are the common medications used by dental practitioners to relieve dental pain and control post-operative signs of inflammation. NSAIDs, irrespective of their benefits, have a lot of hazards because of misuse and faulty prescriptions by dentists. The aim of this study is to evaluate the current use of NSAIDs during dental practice and to evaluate the association of the level of education and years of experience of dental practitioners with the awareness of the safety profile of NSAIDs. This observational cross-sectional study was conducted in Benghazi city between August and October 2024. The sample size is composed of 341 dentists. Participants were selected randomly from approximately every dental clinic in Benghazi. The questionnaire is composed of sections including assessment of drug use and drug-precautionary awareness. It is structured with checklist answers and was formulated in English. It is filled by the dentists during a visit to their dental clinics on the basis of an interview. The Statistics Package for Social Science Version 21 (SPSS) software was used for transferring and analysis of data. The results showed that the females accounted for the majority (60.7%). General practitioners represented 67.7% of the participants. About 61.0% of the dentists had clinical experience of less than 10 years. Ibuprofen and Ketoprofen were the most prescribed NSAIDs, 67.2% and 51.6, respectively. More than fifty percent (55.4%) of the participants used to prescribe NSAIDs for less than three days. Postoperative pain and dental pain were the most common clinical indications that NSAIDs were prescribed, 71.3% and 59.5%, respectively. Pregnancy was the most cited to be contraindicated (58.9%). Awareness of avoiding NSAIDs in the case of peptic ulcer patient was associated with years of experience of the dentists (P=0.030). Participants agreed that nausea was the most side effects (45.2%). Awareness of the interaction between NSAIDs and warfarin was associated with the level of education (P=0.006). The outcomes of the study have revealed less comprehension regarding scientific background knowledge of NSAIDs. There was little effect of level of education and years of experience on the awareness of the safety profile of NSAIDs during dental practice. Therefore, a lot of efforts should be focused on improving the knowledge for making proper therapeutic decisions and minimizing the risk of serious adverse effects on the patients who attend dental clinics.

Metabolomic Profile Modification in the Cerebellum of Mice Repeatedly Exposed to Khat and Treated with β-Lactamase Inhibitor, Clavulanic Acid.

Catha edulis, commonly known as khat, is used for its psychoactive effects and is considered a natural amphetamine. The current study investigated the metabolomic profile in the cerebellum of mice after repeated exposure to khat and evaluated the effects of clavulanic acid on the metabolomic profile in the cerebellum in khat-treated mice. Male C67BL/6 mice that were 6-9 weeks old were recruited and divided into three groups: the control group was treated with 0.9% normal saline for 17 days; the khat group was given khat extract at a dose of 360 mg/kg via the intraperitoneal (i.p) route for 17 days; and another khat group was treated with khat for 17 days and clavulanic acid at a dose of 5 mg/kg for the last 7 days (days 11-17). At the end of the 17th day, the animals were sacrificed, and their brains were immediately collected and stored at -80 °C. The cerebellum region of the brain was isolated in each group by micropuncture using cryostat and underwent a metabolomics study via Gas Chromatography/Mass Spectroscopy (GC/MS). The total peak area ratios of the selected metabolites in the cerebellum after repeated exposure to the khat extract were significantly reduced (p < 0.05) and treatment of the khat group with clavulanic acid significantly increased (all p < 0.05) the total peak areas ratios of the selected metabolites when compared to their corresponding areas in the alternative khat group. These levels of selected metabolites were further confirmed by observing the metabolite peak area ratios and performing a heat map analysis and a principal compartment analysis of the samples in the cerebellum. A network analysis of altered metabolites in the cerebellum showed a strong correlation between the different metabolites, which showed that an increase in one metabolite can modulate the levels of others. An analysis using the MetaboAnalyst software revealed the involvement of selected altered metabolites like lactic acid in many signaling pathways, like gluconeogenesis, while enrichment analysis data showed altered pathways for pyruvate metabolism and disease pathogenesis. Finally, a network analysis showed that selected metabolites were linked with other metabolites, indicating drug-drug interactions. The present study showed that repeated exposure of mice to khat altered the levels of various metabolites in the cerebellum which are involved in the pathogenesis of different diseases, signaling pathways, and interactions with the pharmacokinetic profile of other therapeutic drugs. The treatment of khat-treated mice with clavulanic acid positively modified the metabolomics profile in the cerebellum and increased the levels of the altered metabolites.

Exploiting NRF2-ARE pathway activation in papillary renal cell carcinoma.

Papillary renal cell carcinoma (pRCC) is the second most frequent renal cancer subtype but has no indicated targeted treatments. MET inhibition may be a treatment for MET-driven pRCC, but there is a large group of non-MET-driven pRCC without targeted therapy. Activation of NRF2-ARE pathway has been suggested to be involved in pRCC. To study the relevance of the NRF2-ARE pathway, we characterized 60 pRCCs by copy number analysis and Whole Exome Sequencing. Because stabilisation of NRF2 results in enhanced expression of NQO1, a reductase that prevents production of reactive oxygen species, protein expression of NQO1 was analysed by immunohistochemistry (IHC) from tissue microarrays (TMAs) and by enzymatic activity assay. Finally, patient-derived pRCC cells (PDCs) were applied for drug profiling with 18 NRF2-ARE pathway inhibitors. We identified MET mutations in 5%, and mutations in four genes of NRF2-ARE pathway (NFE2L2, KEAP1, CUL3 and BACH1) in 10% of 60 pRCC samples. IHC analysis of TMAs of 638 renal cancers showed the correlation of the expression of NQO1 with poor survival outcome (p < .001) and high tumour grade (p < .001) and stage (p < .001) in pRCC. NQO1 mRNA, protein levels and enzymatic activity were increased in 56% of matched pRCC tissue samples and patient-derived cells (PDCs, n = 9). Drug screening revealed that Brusatol and Convallatoxin are potential novel drugs for pRCC. Inhibition of NRF2 represents a novel therapeutic approach for MET-independent pRCC patients.

5-Fluorouracil Loaded Prebiotic-Probiotic Liposomes Modulating Gut Microbiota for Improving Colorectal Cancer Chemotherapy.

The gut microbiota exerts inhibitory effects on the occurrence and progression of colorectal cancer (CRC) through various mechanisms. Compared to traditional microbiota regulation methods, prebiotics and probiotics demonstrate significant advantages in terms of safety and patient adaptability. Their synergy not only improves the intestinal environment but also enhances the host's anti-tumor immune response. 5-Fluorouracil (5-FU) is a first-line chemotherapy drug that has a short half-life and low bioavailability. However, if administered in an untargeted manner, 5-FU also causes adverse reactions. Liposomes can improve the pharmacokinetic profile of drugs and provide targeted delivery to the tumor site, thereby reducing side effects. In this work, a 5-FU-loaded liposome is modified with the prebiotic xylan derivative Sxy and the probiotic Akkermansia muciniphila active phospholipid homolog 1,2-dipalmitoylphosphatidy-lethanolamine (DPPE) to construct FLSK. The latter effectively prolongs the intestinal transport and release of 5-FU, maintaining high drug concentrations at the tumor site. FLSK is found to inhibit tumor growth and significantly extends the survival period of mice. In addition, FLSK promotes anti-tumor immunity and regulation of the gut microbiota. Combining the merits of prebiotics and probiotics, FLSK provides a potential strategy for integrating chemotherapy with gut microbiota regulation therapy for the treatment of CRC.

Role of Advance Nuclear Medicine Imaging Techniques in Preclinical Drug Development and Three R's in Animal Research

Preclinical models have played a fundamental role in understanding the pharmacokinetics and biodistribution of novel drugs and radiopharmaceuticals prior to its clinical testing. Application of radiotracers and Nuclear Imaging Techniques have the potential of real time tracking of radiotracer molecules in a non-invasive manner. The three R’s principles are now a worldwide commitment for laboratory animals. Hence, we have carried out PET/CT and scintigraphy imaging technique for monitoring and exploring the in vivo pharmacokinetic profiles of novel drugs in the lung, tumor site, stomach as well as their systemic retention in animals. The present work includes different case studies viz. Evaluation and gastric retention of radiolabeled metformin floating tablet in rabbits by gamma scintigraphy; and Normal biodistribution of radiolabeled etoposide-nano-formulation in New Zealand White rabbit and evaluation of anticancer activity in C57BL/6 mice as a lung metastatic melanoma tumor model. Results showed that the gastric retention of radiolabeled metformin floating tablet was observed to be 50% in the rabbit stomach up to 6h post administration and radiolabeled etoposide-nano-formulation showed 97% of lung uptake in normal rabbit at 1h and significant regression in the number of lung metastasis sites in mice tumor model. Successful drug delivery information can be obtained by in vivo monitoring which enables acquiring statistically significant data from a limited number of animals by the advance imaging modalities. These techniques have an added advantage to provide the 'Reduction' principle in laboratory animals and also boost the research and development for new drugs and radiopharmaceuticals.

Surveillance of Drug Residue Profiles in Gallus gallus domesticus (Silkie Chickens) in Taiwan.

Veterinary drugs are extensively utilized in poultry farming for purposes such as disease prevention, disease treatment, and feed efficiency enhancement. However, the application of these drugs can lead to unacceptable residues in edible products. This study aimed to investigate the residue profiles of veterinary drugs in silkie chickens. A total of 130 chicken samples were collected from two major retail markets in Taiwan between 2022 and 2024. The analysis of drug residues was conducted using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The overall detection rate of drug residues was 57.7%, and most of these residues were found to be below the maximum residue limits. Among the detected drugs, trimethoprim was the most prevalent, followed by nicarbazin, robenidine, decoquinate, diclazuril, and sulfamonomethoxine. Notably, there was a 31.4% chance that different samples from the same flock would yield varying results. Furthermore, a positive correlation was observed between drug residues and sample weight. In conclusion, this study provides valuable epidemiological data on drug residue profiles in silkie chickens in Taiwan. In the future, it is highly recommended that veterinary drug residues be continuously monitored, and food product sampling protocols be adjusted annually to ensure ongoing compliance with safety standards and protect consumer health.

Pharmacovigilance: A Comprehensive Review of Drug Safety Monitoring Practices

Pharmacovigilance, a crucial aspect of healthcare, encompasses the science and activities related to detecting, assessing, understanding, and preventing adverse drug reactions and other drug-related problems1. Its significance has grown considerably, especially following the 1961 thalidomide tragedy, which underscored the need for comprehensive drug safety monitoring. This field plays a vital role in improving patient safety and quality of life, while also safeguarding public health. emphasizes the expanding scope of pharmacovigilance beyond spontaneous reporting and marketed drug evaluation. It now includes ensuring patient safety during clinical trials through informed consent and ethical review boards, developing safety profiles for new drugs, and communicating this information to stakeholders2. Further highlights the importance of pharmacovigilance by discussing consumer reporting of adverse drug reactions and the challenges of early detection. This abstract provides a concise overview of the importance and evolving role of pharmacovigilance in ensuring drug safety

Chronic Use Safety of Agomelatine and Combinations: Impact on Hematological, Biochemical, and Histopathological Parameters in Gender-Specified Rats

Introduction: Polypharmacy may lead to changes in the action profile and toxicity of medicines. Objective: This study evaluated the effect of the association of the antidepressant agomelatine (AGO) with losartan (LOS), simvastatin (SIM), and metformin (MET), after subchronic treatment, on hematological, biochemical, and histopathological parameters in Wistar rats. Methods: The animals were randomly divided into ten groups for each sex and treated for 90 days, per os, with saline, AGO, LOS, SIM, MET, or combinations (AGO+LOS, AGO+SIM, AGO+MET, LOS+SIM+MET, and AGO+LOS+SIM+MET). We evaluated hematological, biochemical, and histopathological parameters. Regarding hematological alterations, the main changes occurred in the erythrogram. Results: Females in polypharmacy were more prone to develop hematological and biochemical alterations. Hepatic and renal functions were the most affected among biochemical parameters. Agomelatine, in association, increased the risk of histopathological changes in males and females, especially in the liver, kidneys, and spleen. Females presented more intense hepatic histopathological changes when AGO was associated with SIM and MET. Females using MET or AGO+MET were more prone to develop histopathological changes than males. The spleen was significantly affected in females, corroborating erythrogram alterations. Conclusion: Agomelatine in association altered the safety profile of drugs, especially in females, indicating caution in their use in polypharmacy with commonly prescribed drugs.

Safety as a determining factor in the pharmaceutical drug development for patients of the pediatric population

Patients in the pediatric population are characterized by differences in the pharmacokinetics and pharmacodynamics of drugs and the range of acceptable dosage forms compared to adult patients. The development of safe drugs is designed to reduce the incidence of adverse reactions in this group. Aim. To highlight physiological features of the body of patients in the pediatric population, the corresponding differences in the pharmacological characteristics of drugs, and approaches to minimizing the risks of pharmacotherapy at the stage of pharmaceutical drug development. Materials and methods. Such general scientific theoretical methods as system analysis, generalization, and system approach, as well as the bibliographic method consisted in processing scientific sources of information on drug use in pediatrics and developing pediatric dosage forms were used. Results. When prescribing drugs to pediatric patients, the physiological features of the child’s body development should be considered, using a flexible approach to pharmacotherapy. Many drugs used in pediatrics have not been officially studied in pediatric clinical trials, and therefore, children often receive them off-label. The use of drugs in pediatrics requires special knowledge about the influence of age-related aspects of the child’s physiology on the absorption, distribution, metabolism and excretion of a drug, as well as on its interaction with receptors and organs. This article discusses approaches to the pharmaceutical development of drugs for use in the pediatric population. Conclusions. In pharmaceutical development of drugs for use in pediatric practice, it is necessary to keep in mind the features of drugs due to age and physiological factors in this category of patients, as well as to take into account the route of administration, the choice of the optimal dosage form, the safety profile of excipients, taste and ease of use of drugs. The development of new medicinal products, including multiparticulate solid dosage forms, is designed to improve the safety profile of drugs in children.