Latest ArticlesTo evaluate the pharmacokinetic characteristics and safety of delafloxacin, a new fluoroquinolone drug, in Chinese healthy subjects, and to evaluate the expected microbiological efficacy of delafloxacin in treating infections caused by Staphylococcus aureus and Streptococcus pneumoniae through pharmacokinetic/pharmacodynamic analysis.
This trial consists of two parts. The first part is a randomized, double-blind, placebo-controlled, single-dose/multiple-dose administration trial with a dose range of 150-450 mg. The second part is a randomized, open-label, double-period, self-crossover trial comparing the pharmacokinetic similarities between a 300 mg intravenous infusion of the test drug and the reference drug. Combined with the in vitro pharmacodynamic data of delafloxacin against Staphylococcus aureus and Streptococcus pneumoniae clinically isolated in China, the Monte Carlo simulation method was used to analyze the probability of target attainment and cumulative fraction of response of the 300 mg q12 h intravenous infusion over 60 min and to evaluate the expected microbiological efficacy.
After administering 150, 300 and 450 mg of delafloxacin to Chinese healthy subjects in single doses, the Cmax, AUC0-t and AUC0-∞ increase proportionally with the dose. The apparent volume of distribution ranged from 45.79 to 144.38 L. The elimination half-life of each dose group ranged from 2.99 to 11.87 h. The cumulative urinary excretion rates of (47.69±8.11)% and (73.71±9.32)% were observed for single doses of 300 and 450 mg, respectively, suggesting that the primary route of excretion was renal. The 90% confidence interval of Cmax, AUC0-t and AUC0-∞ of test drug over reference drug after single-dose intravenous infusion are all within 80.00%-125.00%. After reaching steady state with multiple-dose administration in the 300 mg group, the plasma exposure level was similar to that of the single-dose administration group.
Single-dose intravenous infusion of 150-450 mg delafloxacin in healthy subjects showed linear pharmacokinetic characteristics, and there was no accumulation after 300 mg q12 h administration. Adverse effects were mild, indicating good safety, and good microbiological efficacy.
To establish liquid chromatography-mass spectrometry (LC-MS/MS) quantitative method for determining the blood concentration of Upatinib in human plasma.
Upatinib 15N-d2 was used as the internal standard, and acetonitrile was used for protein precipitation pretreatment. Separate using a Waters BEH C18 (2.4 mm×50.0 mm, 1.7 μm) chromatographic column; acetonitrile (containing 0.1% formic acid) and 0.1% formic acid aqueous solution were used as mobile phases, with gradient elution at a flow rate of 0.3 mL·min-1 and column temperature of 40 ℃. The ion pair used for quantitative analysis was m/z 388.90→255.90 (Upatinib) and m/z 384.10→256.20 (Upatinib-15N-d2, internal standard) respectively by using an electrospray ion source and positive ion multi reaction monitoring mode scanning. The specificity, standard curve, quantitative cutoff, precision, recovery rate, dilution reliability, matrix effect and stability of the method were examined.
There is no mutual interference between endogenous components, internal standards and Upatinib in plasma. The linear relationship between the mass concentration of 0.75-60.00 ng·mL-1 Upatinib and peak area is good (r=0.998 6), the standard curve equation was y=8.24×10-2x+0.61×10-2, with a lower limit of quantification of 0.75 ng·mL-1. The intra-day and inter-day batch precision coefficients of variation of the quality control samples are both ≤5.3%. The accuracy of the sample concentration after 5-fold dilution is 1.1%, and the coefficient of variation is 4.6%. The matrix effect factors of low and high-quality plasma quality control samples are 1.1 and 1.0, respectively. The stability of whole blood samples and plasma samples meets the requirements of biological sample analysis.
The method used is simple, rapid, highly accurate, and sensitive, and is suitable for determining the concentration of Upatinib in human plasma. It can be used for pharmacokinetic and bioequivalence studies of Upatinib in healthy individuals.
To explore the effect of honey-processed Hedysari Radix on the metabolism of short-chain fatty acids (SCFAs) in the cecum of rats with spleen qi deficiency.
A total of 48 SPF male SD rats were randomly divided into blank group, model group, control group and experimental group, with 8 rats in each group. The blank group was fed normally, drank water and ate freely for 15 days, and the other groups used the three-factor composite modeling method of bitter cold diarrhea, overwork and hunger and satiety to construct a spleen qi deficiency model rats for 15 days. After the successful replication of the model, the rats in the control group were given 62.5 mg·kg-1 bifidobacterium Lactobacillus triple viable tablets suspension, the experimental group was given 12.6 g·kg-1 honey-processed Hedysari Radix decoction, and the blank group was given the same dose of distilled water, and the model group continued to model for 15 days. Gas chromatography-mass spectrometry (GC-MS) was used to determine the contents of SCFAs in the cecal contents of rats in each group.
The contents of acetic acid, isobutyric acid, butyric acid, isovaleric acid and caproic acid in the cecal contents of rats in the blank group were (3 706.24±401.84), (99.34±39.11), (2 567.95±529.44), (86.50±54.11) and (393.14±103.33) μg·g-1, respectively. Compared with the blank group, the contents of acetic acid, isobutyric acid, butyric acid, isovaleric acid and caproic acid in the cecum contents of spleen-qi deficiency rats in the model group were significantly reduced, which were (3 049.48±590.62), (67.27±12.99), (2 058.00±417.46), (43.10±11.12) and (27.98±14.40) μg·g-1, respectively (P<0.05, P<0.01). Compared with the model group, the contents of isovaleric acid and caproic acid in the cecum contents of rats in the experimental group were significantly increased, which were (90.59±26.03) and (60.05±19.89) μg·g-1, respectively (all P<0.01).
Honey-processed Hedysari Radix can play a role in strengthening the spleen and replenishing qi by improving the metabolism level of cecal contents, regulating the metabolism levels of SCFAs in cecal contents, protecting the intestinal mucosal barrier, and reducing intestinal inflammation.
National medical insurance drugs and the marketing of new drugs, which support each other, are an important guarantee for clinical patients. In recent years, a series of major reforms have been carried out in national medical insurance drugs, from the dynamic update of the list of medical insurance drugs, to the centralized procurement of drugs, the introduction of national medical insurance negotiation drugs during the agreement period, especially how innovative drugs and original drugs quickly enter the medical insurance, a series of policies and regulations have been issued. Medical students mastering the knowledge of medical insurance drugs is the basis and premise of clinical medication. Pharmacology, as the first path for school medical students to learn drugs, is the important part of cultivating the medical insurance literacy and improving the medical insurance drug audit ability of pharmacology curriculum teaching reform, and also the basis for understanding the correlation of medical insurance drugs and the marketing of new drugs.
Itepekimab is a human immunoglobulin G (IgG)4P monoclonal antibody targeting interleukin-33 (IL-33), currently under development for treating chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD) and bronchial asthma. It has been shown to significantly reduce the incidence of moderate-to-severe acute exacerbations in COPD, lower the rate of uncontrolled asthma, improve lung function, and enhance quality of life. The drug demonstrates a favorable safety and tolerability profile, with common adverse events including headache, nasopharyngitis, gastrointestinal reactions, back pain, and others. This paper provides an overview of the mechanism of action, pharmacokinetics, pharmacodynamics, animal studies, clinical research, and safety profile of Itepekimab.
Doxorubicin is widely used as a first-line therapeutic option in the treatment of several malignant tumors, but its clinical application is severely limited by the dose-dependent and irreversible cardiotoxicity, which has been a long-standing clinical challenge. We analyze the latest clinical guidelines on oncological cardiology and summarize the current status of doxorubicin-induced cardiotoxicity (DIC) prevention and treatment. On this basis, we have gone beyond the traditional view of direct damage to cardiomyocytes, and reviewed the research progress in recent years on the cross-talk between cardiac vascular endothelial cells and cardiomyocytes involved in DIC. The results suggest that cardiac endothelial cells play a key role in the development and maintenance of cardiac function. Doxorubicin not only directly damages these cells, but also disrupts the paracrine signals and physical barriers between them and cardiomyocytes, ultimately leading to an imbalance in cell communication and affecting cardiomyocyte survival and function, resulting in DIC.
Diabetic kidney disease (DKD) is one of the major complications caused by diabetes mellitus, due to its insidious onset, complex pathogenesis and not yet fully defined, it is easy to be delayed for a long period of time to progress to end-stage renal disease (ESRD) or even lead to death. DKD is characterized by the progressive aggravation of urinary protein, and is accompanied by different degrees of glomerulosclerosis, tubular dilatation, interstitial fibrosis and other renal pathologic changes. Data show that hyperglycemic state leads to decreased expression of SIRT1, and SIRT1 has been found to improve renal tissue damage and protect renal function. Therefore, SIRT1 may become a potential target for DKD prevention and treatment, inhibiting renal fibrosis and delaying DKD progression by promoting podocyte autophagy, reducing oxidative stress and inflammatory response. In this paper, we focus on the experimental studies of Chinese medicine extracts targeting the SIRT1 signaling pathway to prevent and control DKD, with a view to providing new ideas and reference basis for the clinical treatment of DKD.
Toll-like receptor 4(TLR4)/ nuclear factor-κB (NF-κB) signaling pathway plays an important role in invasion, proliferation, migration, apoptosis and autophagy of hepatocellular carcinoma cells. Traditional Chinese medicine (TCM) monomers inhibit M2 macrophage polarization, epithelial-mesenchymal transformation (EMT), snail family transcriptional repressor 2 (SLUG) deubiquitination by ubiquitin-specific proteases (USP) and lipopolysaccharide (LPS) -induced cell damage by intervening TLR4/NF-κB signaling pathway. Serum inflammatory chemokine ligand 1(CXCL1) level and cyclooxygenase-2 (COX-2) protein level were significantly decreased and matrixmetalloprotease-9 (MMP-9) protein level was significantly decreased. The expression of MMP-9, decreased the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF), and interfered with mitochondrial membrane potential (MMP), thereby inhibiting tumor cell invasion and migration, and promoting autophagy and apoptosis of hepatoma cells. The main purpose of this review is to update the latest TCM monomer components that exert anti-liver cancer effect through TLR4/NF-κB signaling, and to clarify the main mechanism of their action on liver cancer, and to provide ideas and methods for exploring more TCM with anti-liver cancer properties, so as to better promote the further development and utilization of TCM resources.
Saccharomyces boulardii (S. boulardii), as the sole fungal probiotic, exhibits significant therapeutic efficacy in treating various gastrointestinal disorders. In contrast to traditional bacterial probiotic preparations, S. boulardii stands out for its diverse array of biological activities, including anti-inflammatory, antibacterial, enzymatic, metabolic, and anti-toxin properties. S. boulardii is not indigenous to the human microbiome and is resistant to gastric acid, ensuring its stability and tolerability. Clinical research indicates that S. boulardii offers a positive therapeutic effect in treating gastrointestinal disorders such as acute diarrhea, antibiotic-induced diarrhea, inflammatory bowel disease, and irritable bowel syndrome, while also demonstrating high oral safety. Although the specific mechanisms of action of S. boulardii remain unclear, its clinical efficacy has been widely recognized. This article provides an overview of the advancements in S. boulardii’s application in treating childhood gastrointestinal diseases, serving as a reference for future research directions and clinical applications of this fungus.
The transient receptor potential vanilloid subtype 1 (TRPV1) signaling pathway is closely related to herpes zoster (HZ) and postherpetic neuralgia (PHN). Traditional Chinese medicine (TCM) has been involved in regulating the TRPV1 signaling pathway in several ways, and has been used to treat HZ and PHN by modulating the aberrant release of TRPV1-associated neuropeptides and inflammatory factors, and neurogenic inflammatory response, etc. This paper summarizes the mechanism and role of TCM in regulating TRPV1 signaling pathway in the treatment of HZ and PHN in recent years, which will provide new ideas for the treatment of HZ and PHN and drug development.
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