Current clinical pharmacology最新文献

Background: RNA interference (RNAi) is a process for regulating the gene expression in which small interfering RNAs (siRNAs) silence target genes. siRNA-based therapy as a new molecular treatment approach, offers therapeutic prospects for many common diseases such as cancer and cardiovascular disorders. Nevertheless, the efficacy of siRNA delivery has, so far, remained a challenging issue. This is due to their easy degradation through the circulation system and the difficulties in the intracellular delivery to specific tissues where they silence the target genes. There have been many efforts to develop suitable, safe and effective siRNA delivery systems in the past decades. These efforts specifically aimed to protect siRNA from serum nucleases and deliver it to an intracellular region in the desired target cells. In this context, one of the new and popular approaches is nanovehicle-mediated siRNA delivery systems.

Objective: Here, the authors reviewed and highlighted the recent advances in this exciting and fast growing field to help in the development of effective therapeutic tools in controlling human diseases.

Methods: A literature search was conducted from electronic databases such as Pubmed and Google scholar including original articles and review articles.

Conclusion: siRNA delivery systems potentially may be used in future medicine, particularly for untreatable or poorly treated diseases. As we learn more about these delivery systems, we can better use the tremendous opportunities provided by siRNA-based therapeutics. The results of ongoing clinical trials will play an important role in determining whether siRNA-based drugs can be considered as a new class of drugs.

Background: Monosodium Glutamate (MSG) is one of the most commonly used food additives for the enhancement of food taste and flavour. There are several conflicting reports of toxicity or otherwise safety of the compound, which raises a growing concern regarding the safety of monosodium glutamate as a food additive.

Objective: In the present study, we sought to investigate the effect of monosodium glutamate on body weight, feed consumption, body temperature and some haematological parameters.

Methodology: Twenty adult Wistar rats divided into four groups of five rats each were used for the study. Rats in groups 1, 2 and 3 were given feed thoroughly mixed with 3, 6 and 9 g of monosodium glutamate respectively for 14 days, while rats in group 4 (Control) were given only the feed for the same period of time. Body weight, temperature, feed consumption, and some haematological parameters were measured before the addition of the compound to the feed and thereafter for every 2 days for a period of 14 days.

Results: Our findings indicated significant changes (P < 0.05) in the red blood cells (RBC) count, packed cell volume (PCV), as well as body temperature in all the treated groups compared to the control group. The result also revealed a significant dose-dependent increase in body weight in the groups treated with 6 and 9 g of monosodium glutamate compared to the control, the body weight correlated positively with the duration of monosodium glutamate consumption.

Conclusion: The current data suggest that consumption of high doses/quantity of monosodium glutamate for a long duration of time could lead to anaemia due to a decrease in red blood cell count and packed cell volume and obesity resulting from an increase in body weight gain.

Background: There is an increasing need to face regulatory aspects as well as ethics and scientific ones in the pharmaceutical research phase after the authorization of a drug. Traditionally, Phase IV studies, after the authorization of a drug to be marketed by the Competent Authority like the Food and Drug Administration (FDA) (in Europe, European Medicine Agency - EMA- through National Procedures or Community Procedures) have been considered mainly aimed to the assessment of the new drug safety profile. However, the sample size calculation for such aim is still an open issue. Moreover, the benefit/risk assessment is a compelling global need.

Methods: This editorial aims to give a fairly exhaustive overview of the main topics currently present in the pharmaceutical research phase after the authorization of a drug. FDA and EMA guidelines are considered under a comparative perspective with a focus on the perspective of "Post Authorization Safety Studies (PASS)" and "Post Authorization Efficacy Studies (PAES)" with critical considerations. Then, the approach of "Explanatory Trials" and "Pragmatic Trials" is proposed under the horizon of Health Technology Assessment (HTA).

Conclusion: Critical remarks are raised against the pure commercial perspective in the proposal of PASS and PAES and on the design of registries which should be planned with relevant objectives to be pursued by appropriate statistical analyses reported in the Statistical Analysis Plan (SAP) of the study protocol. Finally, a particular focus is placed on the work of the Ethical Committees regarding the approval of the observational studies on the safety and the efficacy of the drugs in their pragmatic clinical use.

Background: Irritable bowel syndrome (IBS) is the most frequently diagnosed functional gastrointestinal disorder. It is characterised by abdominal pain, bloating and changes in bowel habits that can have a serious impact on the patient's quality of life. Treatment strategies are based on the nature and severity of the symptoms, the degree of functional impairment of the bowel habits, and the presence of psychosocial disorders. The purpose of this review is to update our current knowledge of therapeutic approach of this disorder.

Method: A literature search for IBS therapy was carried out using the online databases of Pubmed, Medline and Cochrane.

Results: An ideal treatment begins by explaining this condition and providing reassurance to the patients. There is limited evidence for the efficacy, and tolerability of the therapies currently available for the treatment of IBS. There is also a limited availability of pharmacological agents licensed specifically for the treatment of IBS subtypes, although new agents have been recently proposed to this goal. Furthermore, patients often associate their complaints with the ingestion of foods containing FODMAPs (fermentable oligo-di-monosaccharides, and polyols) and gluten derivates and a personalized diet can be proposed. However, more severe symptoms can be associated with greater levels of psychosocial problems and a psychological approach and antidepressant drugs can be needed.

Conclusion: The treatment of IBS remains focused on treating the patient's predominant, or most troublesome, symptoms. New promising treatments have recently become available for the treatment of IBS but long term studies are still needed.

Background: Acne vulgaris is a common dermatologic disorder which results in psychological consequences. Inflammatory responses play an important role in the development of inflammatory acne lesions. Recently, many studies have demonstrated anti-inflammatory effects of statins; thus, the aim of this study was to evaluate the efficacy of oral and topical Simvastatin as adjunct therapy in the treatment of acne vulgaris.

Methods: A total of 76 patients with moderate to very severe acne vulgaris, all receiving oral azithromycin (250 mg, 3 times a week, orally) and topical benzoyl peroxide gel (5%, once daily) were assigned to three groups: 1) Oral group received 20mg/day of oral simvastatin and blank solution, 2) Topical group received simvastatin 1% topical solution and oral placebo, 3) Placebo group received oral placebo and blank solution. The severity of acne was determined by global acne grading system (GAGS) at baseline and after 8 weeks of treatment.

Results: Comparing the three groups showed that topical simvastatin was associated with greater decrease in acne severity as compared with those of oral and placebo groups. Moreover, the oral simvastatin appeared to be more efficacious as compared with placebo group (P value<0.001). Oral and topical simvastatin were well tolerated in almost all patients.

Conclusion: Although preliminary, the results of this study showed that oral and topical statins, drugs with anti-inflammatory properties, can be considered as effective treatment for acne vulgaris as an adjunct to standard treatment. However, further studies with larger sample size, using improved formulations of topical simvastatin are needed to confirm these results.

Introduction: Pharmacovigilance (PV) is the science responsible for ADRs reporting and accordingly medication safety. Pediatrics age group is a special concern as they have a higher risk of developing ADRs; this put more burden on pediatricians for early detection and reporting of ADRs. The present study aims to explore pediatricians' knowledge, attitude, and practices of pharmacovigilance.

Method: A structured validated questionnaire was designed to achieve the study goals. A convenient sample of 142 pediatricians took part in the study.

Results: The majority of pediatricians had a poor knowledge score about pharmacovigiliance and ADRs reporting. On the other hand, 71% of respondents had a good attitude score towards reporting ADRs. When exploring their own practice, pediatricians have a low reporting rate.

Conclusion: The results of the present study reveal that pediatricians lack knowledge of PV and ADRs reporting. However, they have a good attitude towards ADRs reporting and enhancing their PV practice. This is still not reflected in their own practice. Further training and education about ADRs reporting are very important to move toward safer medications in children.

Background: The liver is the major metabolic clearance organ for chemical agents from the human body. Pregnancy is associated with several physiological changes that may affect one or more of these factors, and also induces changes in the hepatic clearance of certain drugs. The aim of this paper was to review some of the currently available information in the field to provide some insights about the relevance of these changes on the clearance of some drugs.

Methods: A comprehensive literature search was carried out to identify eligible studies from MEDLINE/PubMed, EMBASE and SCIELO databases through 1970 first semester.

Results: Gestational Diabetes Mellitus (GDM) is a frequent disease commonly associated with other entities as obesity, hypertension, dyslipidemia, non-alcoholic fatty liver disease, prothrombotic conditions, changes in intestinal microbiome. These entities, together with the glycemic fluctuations associated with GDM might affect the determinants of the hepatic clearance (hepatic blood flow, the unbound fraction of drugs, and the hepatic intrinsic clearance). GDM is frequently associated with multi-drug treatments. While many of these drugs are cleared by the liver, little is known about the clinical relevance of these GDM associated pharmacokinetic changes.

Conclusion: Considering the frequency of the disease and the effects that these pharmacokinetic changes might have on the mother and child, the need for further research seems advisable. In the meantime, cautious clinical judgment in the management of drug administration in women affected by this disease is recommended.

Background: Lupus nephritis (LN) is a common complication in many patients with systemic lupus erythematosus, although renal-limited lupus nephritis has been reported as well. Early diagnosis of lupus nephritis is critical as early detection and effective treatment can improve renal outcomes in such patients.

Objective: The treatment of lupus nephritis is largely determined based on the histological class present on the renal biopsy specimen. In most cases, Class I and II of lupus nephritis do not require any specific treatment, but class III and IV lupus nephritis require immunosuppressive therapy. Treatment of Class V and VI remains controversial. In 2012, six guidelines were introduced for the management of lupus nephritis. These guidelines offer comprehensive treatment plans for each class of Lupus nephritis but differ from each other in many aspects. The purpose of this article is to review the current literature of the available pharmacological treatments used in the six classes of lupus nephritis as well as resistant lupus nephritis, strategies to address the problems of inadequate therapeutic response, medication related side effects, relapses of lupus nephritis, and some future treatment options.

Methods: We reviewed the available literature and treatment guidelines on lupus nephritis in detail to present a comprehensive review of the available treatment options for different classes of lupus nephritis.

Conclusion: Lupus nephritis which does not respond to initial treatment is associated with worse renal outcomes. Several therapeutic approaches are available for the induction and maintenance immunosuppression of the different classes of LN. Management of LN should be individualized for each patient based on their risk-benefit profile.

Background: Drug development for rare diseases is challenging because it is difficult to obtain relevant data from very few patients. It must be informative to grasp current status of clinical trials for drug development in rare diseases.

Objective: Clinical trials in rare diseases are to be outlined and compared among the US, EU and Japan.

Method: ClinicalTrials.gov (NCT, National Clinical Trial), EU Clinical Trials Register (EUCTR) and the Japan Primary Registries Network (JPRN) were analyzed. Clinical trials involving information on rare diseases and drugs were extracted by text-mining, based on the diseases and drugs derived from Orphanet and DrugBank, respectively.

Results: In total, 28,526 clinical trials were extracted, which studied 1,535 rare diseases and 1,539 drugs. NCT had the largest number of trials, involving 1,252 diseases and 1,332 drugs. EUCTR and JPRN also had registry-specific diseases (250 and 22, respectively) and drugs (172 and 29, respectively) that should not be missed. Among the 1,535 rare diseases, most diseases were studied in only a limited number of trials; 70% of diseases were studied in fewer than 10 trials, and 28% were studied in only one. Additionally, most studied rare diseases were cancer-related ones.

Conclusion: This study has revealed the characteristics of the clinical trials in rare diseases among the US, EU and Japan. The number of trials for rare diseases was limited especially for non-cancerrelated ones. This information could contribute to drug development such as drug-repositioning in rare diseases.

Oxidative stress is a major mechanism underlying the development of various neurodegenerative diseases (Alzheimer, Parkinson, Huntington and amyotrophic lateral sclerosis). Excessive formation of reactive oxygen species (ROS) and nitrogen (RNSs) can overburden the ability of the enzymatic antioxidant defense mechanisms (superoxide dismutase, catalase and glutathione reductase) and non-enzymatic (uric acid, ascorbic acid, α-tocopherol and reduced glutathione), causing the development of oxidative stress, and consequently, impairing the neuronal system cells by means of oxidative damage to a variety of important biological molecules such as lipids, DNA and proteins. Considering the importance of oxidative stress in neurodegenerative diseases, the present review aims to address the main parameters evaluated in in vitro studies on oxidative stress in different models of neurodegenerative diseases.The literary review was conducted through Pubmed, Science Direct, LILACS, Scielo and Google using following keywords: oxidative stress, neurodegenerative diseases and parameters of oxidative stress. We selected articles published between 2002 and 2017.The in vitro evaluation of the oxidative stress related parameters has provided a preliminary view about the pathogenesis of many neurodegenerative diseases (Alzheimer's, Parkinson's, Huntington's and Amyotrophic lateral sclerosis). In this way, it has demonstrated the mechanism of action of ROS/RNSs in these diseases by direct or indirect detection through several experimental procedures in vitro.