1.Comparison of efficacy,safety and economics of bid-winning and original Moxifloxacin hydrochloride tablets in the treatment of outpatient community-acquired pneumonia
Jie PANG ; Xiaowen WU ; Chunhua LI ; Taiyu JIN ; Weili YOU
China Pharmacy 2023;34(2):200-204
OBJECTIVE To compare the efficacy, safety and economics of bid-winning and original Moxifloxacin hydrochloride tablets in the treatment of outpatient community-acquired pneumonia (CAP). METHODS A retrospective cohort study was conducted to screen and include CAP outpatients during the period of January to December 2021 in Lianyungang First People’s Hospital. They were divided into generic drug group (1 058 cases) and bid-winning drug group (1 121 cases) according to the drug source. Two groups were respectively given original and bid-winning Moxifloxacin hydrochloride tablets, 0.4 g each time, once a day. The efficacy indexes (clinical effective rate, remission time, treatment course, revisiting rate) and safety indexes (allergy, nervous system symptoms, etc.) were compared between the two groups; and the influence factors of clinical treatment failure were analyzed with multi-factor modified Poisson regression model. The economic indicators of the two drugs [quantity, consumption sum, defined daily doses (DDDs), defined daily dose cost (DDDc), price ratio, replacement rate] were compared. RESULTS There were no significant differences in the clinical effective rate, treatment course, revisiting rate, the incidence of nervous system symptoms and Q-T interval prolongation between the two groups (P>0.05). The remission time of original drug group was significantly shorter than that of bid-winning drug group, and the incidence of total adverse drug reaction, allergy reaction, gastrointestinal symptom reaction and hyperglycemia were significantly lower than those in bid-winning drug group(P<0.05). Multivariate Poisson regression analysis showed that bid-winning drug did not increase the risk of clinical treatment failure in CAP outpatients [RR=1.132, 95%CI (0.883, 1.542), P=0.327]. However, antibiotic exposure history, more than 2 items of abnormal clinical manifestations and auxiliary examination all increased the risk of clinical treatment failure (P<0.05). Compared with before the implementation of centralized volume-based procurement policy, the quantity and DDDs of Moxifloxacin hydrochloride tablets increased significantly, while the consumption sum decreased significantly, DDDc of bid-winning drug decreased significantly, the price ratio of it to original drug decreased to 0.117, and the replacement rate increased to 69.44% after the implementation of centralized volume- based procurement policy. CONCLUSIONS Compared with original drug, bid-winning Moxifloxacin hydrochloride tablet shows reliable efficacy and obvious price advantage in the treatment of outpatient CAP, but the incidence of adverse drug reactions is higher.
2.Nuciferine protects against high-fat diet-induced hepatic steatosis and insulin resistance via activating TFEB-mediated autophagy-lysosomal pathway.
Xiliang DU ; Chiara DI MALTA ; Zhiyuan FANG ; Taiyu SHEN ; Xiaodi NIU ; Meng CHEN ; Bo JIN ; Hao YU ; Lin LEI ; Wenwen GAO ; Yuxiang SONG ; Zhe WANG ; Chuang XU ; Zhijun CAO ; Guowen LIU ; Xinwei LI
Acta Pharmaceutica Sinica B 2022;12(6):2869-2886
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy-lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.