Aclidinium bromide and formoterol fumarate for the maintenance treatment of chronic obstructive pulmonary disease

ABSTRACT

Introduction: Treatment options for COPD have evolved rapidly in the last decade and inhaled bronchodilators have largely supplanted the use of oral bronchodilators because of their increased efficacy and excellent safety with topical delivery to the lung. Recently added to the therapeutic armamentarium are fixed-dose combinations (FDC) of two long acting bronchodilators. LAMAs (long acting muscarinic antagonists) and LABAs (long acting beta agonists) are the main classes available and use different pathways to effectively produce bronchial smooth muscle relaxation.

Areas covered: The most recent inhaled FDC LAMA/LABA to come to market is Aclidinium Bromide and Formoterol Fumarate. We searched databases of PubMed, Cochrane Library, and manufacturers’ websites and retrieved all the randomized-controlled trials (RCTs) conducted with these drugs up to September 2019.

Expert opinion: It is likely that FDCs will become the core of our COPD pharmacotherapy for all but the mildest COPD patients. These individual drugs have excellent efficacy and safety records for the maintenance treatment of COPD. Studies have demonstrated that twice daily treatment with aclidinium/formoterol resulted in significant improvement in lung function and an improved exercise tolerance when compared to placebo. Adverse effects are within the range of what is seen with other LAMA/LABA combinations.     

The potential role of nicotinamide on Leishmania tropica: An assessment of inhibitory effect,cytokines gene expression and arginase profiling

Leishmaniasis represents a major health concern worldwide which has no effective treatment modality. Nicotinamide (NAm) has been used for a wide range of applications from anticancer to antimicrobial usage. This study aimed to assess the effect of NAm combination on Leishmania tropica Inhibition, as well as on cytokines gene expression and arginase (ARG) activity in L. tropica-infected macrophages in an in vitro model. The leishmanicidal effects of NAm and Glucantime (meglumine antimoniate, MA) alone and in combination (NAm/MA) were evaluated using a colorimetric assay and macrophage model. Additionally, immunomodulatory effects and enzymatic activity were assessed by analyzing Th1 and Th2 cytokines gene expression and ARG level, respectively, in infected macrophages treated with NAm and MA, alone and in combination. Findings indicated that the NAm/MA combination demonstrated greater inhibitory effects on L. tropica promastigotes and amastigotes compared with each drug individually. Docking results proved the affinity of NAm to IFN-γ, which can affirm the increased levels of IFN-γ, IL-12p40 and TNF-α as well as reductions in IL-10 secretion with a dose-response effect, especially in the combination group. The NAm/MA combination also showed a significant reduction in the level of ARG activity at all concentrations used compared to each drug individually. These findings indicate higher effectiveness of NAm plus MA in reducing parasite growth, promoting immune response and inhibiting ARG level. This combination should be considered as a potential therapeutic regimen for treatment of volunteer patients with anthroponotic cutaneous leishmaniasis (ACL) in future control programs.     

基于关联规则对缺血性脑卒中住院患者联合用药分析*

目的：了解缺血性脑卒中患者的一般基础情况、合并疾病及临床药物联合使用特征。方法：运用回顾性分析法,对医院信息系统数据库中部分缺血性脑卒中住院患者病历进行分析。采用频数分析法对患者的基本信息进行描述性统计,运用关联规则分析方法统计常用药物二联、三联等使用情况。结果：缺血性脑卒中患者多为老年人,男性较多,常合并高血压、冠心病和糖尿病等疾病。该类患者临床用药中,硫酸氢氯吡格雷联合阿托伐他汀钙使用最多;使用阿托伐他汀钙和前列地尔的患者中,同时使用硫酸氢氯吡格雷最多。在使用抗心绞痛药的患者中,使用抗血小板药的概率最高;在同时使用抗心绞痛药和调血脂药的患者中,使用抗血小板药的概率最高。结论：在缺血性脑卒中患者临床治疗中,抗血小板药、降血压药、调血脂药、活血化瘀药和血管扩张药常一起联合使用,如阿司匹林、瑞舒伐他汀钙、硫酸氢氯吡格雷、前列地尔和美托洛尔最可能合并使用。     

Dopamine increases the anti-cancer efficacy of sunitinib in the treatment of pancreatic cancer

Sunitinib (SUN) is a multi-targeted receptor tyrosine kinase inhibitor (TKI) that may lead to drug resistance and metastasis because of increased cancer stem-like cells (CSCs) due to the induction of hypoxia. Our group has proved that dopamine (DA) can specifically reduce CSC frequency and enhance the response of SUN in drug-resistant breast cancerand non-small cell lung cancer (NSCLC). In this study, DA and SUN combination therapy was investigated in the treatment of pancreatic cancer, a malignant tumor with high mortality rate and very limited therapies. The cytotoxicity assay, clone formation assay and wound healing assay in two pancreatic cancer cell line PANC-1 and SW1990 showed that DA could significantly increase the effect of SUN on cell survival, clone formation ability and migration ability. Besides, SW1990 cell-derived xenograft model and a pancreatic cancer patient-derived xenograft (PDX) model were constructed, further proving that DA could increase the in vivo anti-tumor efficacy of SUN, and could be reversed by SCH23390, a D1 dopamine receptor (D1DR) antagonist. Moreover, the CSC frequency of the combination groups was lower than the control groups or SUN monotherapy groups. In addition, the body weight, H&E staining and blood routine test results showed that the combination therapy was safe. In summary, DA and SUN combination therapy could be a promising strategy for the treatment of pancreatic cancer.     

Clinical study of repaglinide efficacy and safety in type 2 diabetes mellitus patients with blood glucose levels inadequately controlled by sitagliptin

Aims/Introduction

The aim of the present study was to evaluate the long‐term efficacy and safety of adding repaglinide in patients with type 2 diabetes mellitus whose blood glucose levels were not sufficiently controlled by treatment with a dipeptidyl peptidase‐4 inhibitor, sitagliptin, in addition to diet and exercise therapies.

Materials and Methods

This was a multicenter, uncontrolled, dose‐titration study with a treatment period of 52 weeks. The primary end‐point was the change in glycated hemoglobin levels from baseline.

Results

The glycated hemoglobin level was 7.43 ± 0.57% (mean ± standard deviation) at baseline, and decreased to 6.93 ± 0.91% at the end of the study. The mean changes in glycated hemoglobin levels at 4 weeks and at the end of the study were −0.44 ± 0.28% and −0.50 ± 0.82%, respectively. The glycated hemoglobin‐lowering effect was maintained for 52 weeks. The rate of adverse events was 86.0% (86/100), and there were 352 adverse events. The rate of adverse drug reactions was 21.0% (21/100). Hypoglycemia was reported in 5.0% (5/100) of patients, but there was no incidence of ‘major hypoglycemia’.

Conclusions

Combination therapy with repaglinide and sitagliptin was considered effective for a long term without clinical safety problems in patients with type 2 diabetes mellitus.     

冷冻联合氩气刀介入治疗恶性气道狭窄的临床观察

目的：探讨冷冻联合氩气刀介入治疗恶性气道狭窄的临床疗效及安全性。方法根据介入治疗方法的不同,将40例恶性气道狭窄患者分为两组。 A组(22例)使用冷冻联合氩气刀治疗,B组(18例)使用单纯冷冻治疗,评价两组治疗方法的临床疗效及并发症情况。结果 A组患者再通有效率为95．45%,明显高于B组(66．67%),差异有统计学意义( P<0．05);两组患者未见严重不良反应及并发症。结论冷冻联合氩气刀治疗恶性气道狭窄疗效可靠并安全,优于单纯冷冻治疗,值得临床推广应用。     

Relative Bioavailability of Rifampicin in Four Chinese Fixed-dose Combinations Compared with Rifampicin in Free Combinations

Background:

Decreases in the bioavailability of rifampicin (RFP) can lead to the development of drug resistance and treatment failure. Therefore, we investigated the relative bioavailability of RFP from one four-drug fixed-dose combination (FDC; formulation A) and three two-drug FDCs (formulations B, C, and D) used in China, compared with RFP in free combinations of these drugs (reference), in healthy volunteers.

Methods:

Eighteen and twenty healthy Chinese male volunteers participated in two open-label, randomized two-period crossover (formulations A and C) or one three-period crossover (formulations B and D) study, respectively. The washout period between treatments was 7 days. Bioequivalence was assessed based on 90% confidence intervals, according to two one-sided t-tests. All analyses were done with DAS 3.1.5 (Mathematical Pharmacology Professional Committee of China, Shanghai, China).

Results:

Mean pharmacokinetic parameter values of RFP obtained for formulations A, B, C, and D products were 11.42 ± 3.41 μg/ml, 7.86 ± 5.78 μg/ml, 13.05 ± 6.80 μg/ml, and 16.18 ± 3.87 μg/ml, respectively, for peak plasma concentration (C_max), 91.43 ± 30.82 μg·h⁻¹ ·ml⁻¹, 55.49 ± 37.58 μg·h⁻¹ ·ml⁻¹, 96.50 ± 47.24 μg·h⁻¹ ·ml⁻¹, 101.47 ± 33.07 μg·h⁻¹ ·ml⁻¹, respectively, for area under the concentration-time curve (AUC_{0−24 h}).

Conclusions:

Although the concentrations of RFP for formulations A, C, and D were within the reported acceptable therapeutic range, only formulation A was bioequivalent to the reference product. The three two-drug FDCs (formulations B, C and D) displayed inferior RFP bioavailability compared with the reference (Chinese Clinical Trials registration number: ChiCTR-TTRCC-12002451).     

Epinephrine injection therapy versus a combination of epinepnrine injection and endoscopic hemoclip in the treatment of bleeding ulcers

AIM: To assess the efficacy of hemoclip application in combination with epinephrine injection in the treatment of bleeding peptic ulcers and to compare the clinical outcomes between patients treated with such a combination therapy and those treated with epinephrine injection alone. METHODS: A total of 293 patients (211 males, 82 females) underwent endoscopic therapy for bleeding peptic ulcers. Of these, 202 patients (152 males, 50 females) received epinephrine injection therapy while 91 patients (59 males, 32 females) received combination therapy. The choice of endoscopic therapy was made by the endoscopist. Hemostatic rates, rebleeding rates, need for emergency surgery and 30-d mortality were the outcome measures studied. RESULTS: Patients who received combination therapy were significantly older (mean age 66±16 years, range 24-90 years) and more suffered from chronic renal failure compared to those who received epinephrine injection therapy alone (mean age 61±17 years, range 21-89 years). Failure to achieve permanent hemostasis was 4% in the group who received epinephrine injection alone and 11% in the group who received combination therapy. When the differences in age and renal function between the two treatment groups were taken into account by multivariate analysis, the rates of initial hemostasis, rebleeding rates, need for surgery and 30-d mortality for both treatment options were not significantly different. CONCLUSION: Combination therapy of epinephrine injection with endoscopic hemoclip application is an effective method of achieving hemostasis in bleeding peptic ulcer diseases. However, superiority of combination therapy over epinephrine injection alone, could not be demonstrated.