229 research outputs found
DNA (cytosine-5)-methyltransferase 1 as a mediator of mutant p53-determined p16(ink4A) down-regulation
No full textSynthesis and electrochemical properties of Li-rich Li[Ni0.5Co0.2Mn0.3]O2 for pouch-typed cell
No full textPharmacokinetics and Bioequivalence of Apremilast Tablets in Chinese Healthy Subjects Under Fasting and Postprandial States
Full text linkWanjun Bai,1 Xue Sun,1 Bo Qiu,1 Caihui Guo,1 Haojing Song,1 Yiting Hu,1 Xueyuan Zhang,2 Peihua Yin,3 Xiaoru Wang,3 Zhanjun Dong1 1Department of Pharmacy, Hebei General Hospital, Hebei Key Laboratory of Clinical Pharmacy, Shijiazhuang, Hebei, People’s Republic of China; 2Center for Clinical Pharmacology, Shanghai Innovstone Therapeutics Limited, Shanghai, People’s Republic of China; 3Center for Clinical Pharmacology, CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd, Shijiazhuang, People’s Republic of ChinaCorrespondence: Zhanjun Dong, Department of Pharmacy, Hebei General Hospital, Hebei Key Laboratory of Clinical Pharmacy, No. 348 Heping West Road, Xinhua District, Shijiazhuang City, Hebei Province, 050051, People’s Republic of China, Tel +86 311 85988604, Email [email protected]: This study compared the pharmacokinetics, safety and bioequivalence (BE) of generic and original apremilast tablets in healthy Chinese subjects under fasting and postprandial conditions, providing sufficient evidence for abbreviated new drug application.Methods: A randomized, open-label, two-formulation, single-dose, two-period crossover pharmacokinetic study was performed. Thirty-two eligible healthy Chinese subjects were enrolled in fasting and postprandial studies, respectively. In each trial, subjects received a single 30-mg dose of the test or reference apremilast tablet, followed by a 7-day washout interval between periods. Serial blood samples were obtained for up to 48 h post-intake in each period, and the plasma concentrations of apremilast were determined by a validated method. The primary pharmacokinetic (PK) parameters, including the maximum plasma concentration (Cmax), the areas under the plasma concentration–time curve (AUC0-t, AUC0-∞), were calculated using the non-compartmental method. The geometric mean ratios of the two formulations and the corresponding 90% confidence intervals (CIs) were acquired for bioequivalence analysis. The safety of both formulations was also evaluated.Results: Under fasting and postprandial states, the PK parameters of the test drug were similar to those of the reference drug. The 90% CIs of the geometric mean ratios of the test to reference formulations were 94.09– 103.44% for Cmax, 94.05– 103.51% for AUC0-t, and 94.56– 103.86% for AUC0-∞ under fasting conditions, and 99.18– 112.48% for Cmax, 98.79– 106.02% for AUC0-t, and 98.95– 105.89% for AUC0-∞ under postprandial conditions, all of which were within the bioequivalence range of 80.00– 125.00%. Both formulations were well tolerated, and no serious adverse events occurred during the study.Conclusion: The trial confirmed that the PK parameters of the generic and original apremilast tablets were bioequivalent in healthy Chinese subjects under fasting and postprandial states, which met the predetermined regulatory standards. Both formulations were safe and well tolerated.Clinical Trial Registration: chinaDrugtrials.org.cn, identifier CTR20191056 (July 30, 2019); chictr.org.cn, identifier ChiCTR2300076806 (October 19, 2023).Keywords: apremilast, psoriasis, pharmacokinetics, bioequivalence, safet
Bioequivalence Study of Vortioxetine Hydrobromide Tablets in Healthy Chinese Subjects Under Fasting and Fed Conditions
No full textWanjun Bai,1 Haojing Song,1 Yiting Hu,1 Xueyuan Zhang,2 Xiaoru Wang,3 Caihui Guo,1 Bo Qiu,1 Zhanjun Dong1 1Department of Pharmacy, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 2Shanghai Innovstone Therapeutics Limited, Shanghai, People’s Republic of China; 3CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd, Shijiazhuang, People’s Republic of ChinaCorrespondence: Zhanjun Dong, Department of Pharmacy, Hebei General Hospital, No. 348 Heping West Road, Xinhua District, Shijiazhuang City, Hebei Province, 050051, People’s Republic of China, Tel +86 311 85988604, Email [email protected]: This study compared the pharmacokinetic and safety profiles of generic and original vortioxetine hydrobromide tablets under fasting and fed conditions, and evaluated the bioequivalence of two vortioxetine formulations to obtain sufficient evidence for abbreviated new drug application.Methods: A randomized, open-label, two-formulation, single-dose, two-period crossover bioequivalence study was conducted under fasting and fed conditions (n = 32 per study). Eligible healthy Chinese subjects received a single 10-mg dose of the test or reference vortioxetine hydrobromide tablet, followed by a 28-day washout interval between periods. Serial blood samples were collected up to 72 h after administration in each period, and the plasma concentrations of vortioxetine were detected using a validated method. The primary pharmacokinetic (PK) parameters were calculated using the non-compartmental method. The geometric mean ratios for the PK parameters of the test drug to the reference drug and the corresponding 90% confidence intervals were acquired for bioequivalence analysis. A safety evaluation was performed throughout the study.Results: Under fasting and fed conditions, the PK parameters of the test drug were similar to those of the reference drug. The 90% confidence intervals (CIs) of the geometric mean ratios of the test to reference formulations were 96.44– 105.81% for peak concentration (Cmax), 97.94– 105.05% for the area under the curve truncated at 72 hours (AUC0-72 h) under fasting conditions, 93.92– 104.15% for Cmax, and 96.67– 102.55% for AUC0-72 h under fed conditions, all of which were within the accepted bioequivalence range of 80.00– 125.00%. Both the test and reference formulations were well-tolerated, and no serious adverse events related to the study drug were reported during the study.Conclusion: The PK bioequivalence of the test and reference vortioxetine hydrobromide tablets in healthy Chinese subjects was established under fasting and fed conditions, which met the predetermined regulatory criteria. Both formulations were safe and well tolerated.Keywords: vortioxetine, bioequivalence, pharmacokinetics, safet
Pouch-typed cell from Li-rich LiFePO4 prepared by low-cost carbothermal reduction method
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Microwave-assisted solvothermal synthesis and performances of LiMn<sub>0.7</sub>Fe<sub>0.3</sub>PO<sub>4</sub> nanoplates
No full textCalcium, Ammonia, Redox-Active Tyrosine YZ, and Proton-Coupled Electron Transfer in the Photosynthetic Oxygen-Evolving Complex
No full textImmune-Related Adverse Event-Related Adrenal Insufficiency Mediates Immune Checkpoint Inhibitors Efficacy in Cancer Treatment
No full textShasha Zhang,1,* Jianhua Wu,2,* Yue Zhao,3 Jingjing Zhang,1 Xiaoyun Zhang,1 Chensi Wu,3 Zhidong Zhang,4 Zhanjun Guo1 1Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China; 2Animal Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China; 3Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China; 4Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhidong Zhang, Department of Surgery, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, People’s Republic of China, Email [email protected] Zhanjun Guo, Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, People’s Republic of China, Tel +86 311 86095734, Email [email protected]: Immune checkpoint inhibitors (ICIs) have significantly improved the outcomes of patients with cancer; however, these agents may initiate immune-related adverse events (irAEs). Previous studies have demonstrated a robust correlation between disease prognosis and the occurrence of irAEs, specifically skin or endocrine irAEs. Herein, we aimed to evaluate the correlation between irAE-related adrenal insufficiency (AI) and ICI treatment efficacy.Patients and methods: Patients diagnosed with gastrointestinal, respiratory, head and neck, urological, skin and gynecologic cancers treated with anti-programmed cell death 1 (PD-1)/anti-programmed cell death ligand 1 (PD-L1) antibody as monotherapy or combined therapy (combined with chemotherapy or targeted therapy) were divided into irAE-A (patients with irAE-related AI), irAE-B (patients with other irAEs) and non-irAE groups. Immunotherapy efficacy was assessed based on the disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Survival probabilities were estimated using the Kaplan–Meier method with the log–rank test.Results: Of the 192 patients enrolled in our study, 17 developed irAE-related AI and 83 developed other irAEs. The DCR of the irAE-A and irAE-B groups were higher than that of the non-irAE group (P< 0.05). Multiple extended Cox regression analyses showed that irAE status (irAE-A vs non-irAE, P=0.008; irAE-B vs non-irAE, P=0.020), Eastern Cooperative Oncology Group (ECOG) status (P=0.045), tumor-node-metastasis (TNM) stage (P=0.000), and treatment line (P=0.002) were independent predictors of PFS. Contrarily, irAE status (irAE-A vs non-irAE, P=0.009; irAE-B vs non-irAE, P=0.013), ECOG status (P=0.007), TNM stage (P=0.035), treatment line (P=0.001) and treatment modality (P=0.008) were independent predictors for OS.Conclusion: IrAE-related AI was significantly associated with ICI treatment efficacy in patients with cancer, which could be a potentially predictable marker. Due to the destruction of adrenal tissue by T cells with enhanced activity, AI reflects enhanced T cell activity to some extent.Keywords: endocrine adverse event, malignancies, monoclonal antibody therapy, immune-related side effects, treatment efficac
Viscous Flow and Crystallization Behaviors of P-bearing Steelmaking Slags with Varying Fluorine Content
No full textThe role of fluorine in the CaO-SiO2-MgO-Al2O3-FetO steelmaking slags was investigated through analyzing the viscous flow and crystallization behaviors of the slags. It was found that the viscosity decreased with increasing CaF2 content, which resulted from the decrease of the degree of polymerization (DOP) of the structures, as proved by O-1s X-ray photoelectron spectroscopy (XPS) and magic angular spinning nuclear magnetic resonance (MAS-NMR) analysis. The continuous cooling transformation (CCT) diagrams of the primary crystals were also constructed. The results showed that CaF2 addition promoted the transformation of the primary crystal from spinet (MgFe2O4) to flourapatite (Ca-5(PO4)(3)F), which was beneficial to the further enrichment of phosphorus. According to F-19 MAS-NMR results, F- ions mainly coordinate with Ca2+ ions to form Ca-F bond. Furthermore, considering the greater stability of P-O-Ca than that of Si-O-Ca bonds, most of the F- ions behave as F-Ca-O-P band, which thus enhanced the formation of Ca-5(PO4)(3)F. Additionally, the non-isothermal crystallization kinetics was further analyzed and the activation energy for the primary crystal growth was derived.National Natural Science Foundation of China [51522401, 51472007, 51372019]; National High Technology Research and Development Program of China (863 Program) [2012AA06A114]SCI(E)[email protected]; [email protected]
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