Latest ArticlesTo explore post-marketing adverse drug events (ADE) of avacopan and explore the risk factors for severe ADE, providing a reference for clinical safe and rational drug use.
Retrieved adverse event report information associated with avacopan from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database were extracted, covering a total of 12 quarters from the fourth quarter of 2021 to the third quarter of 2024. Suspicious AEs were screened using the reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), multiple item empirical bayesian gamma poisson shrinker (MGPS) based on disproportionality analysis. Univariate and multivariate logistic regression analyses were conducted on severe ADE to explore the risk factors associated with avacopan-induced severe ADE according to their severity.
A total of 2 886 ADE reports associated with avacopan were obtained, including 1 489 reports of severe AEs. Using the disproportionality analysis methods, a total of 69 positive ADE signals were identified for avacopan, involving 14 systems and organs. The ADE associated with avacopan were sorted by frequency of occurrence, with hospitalisation (272 cases) having the highest number of reports. By signal strength, antineutrophil cytoplasmic antibody increased showed the strongest signal (ROR=290.83, 95%CI=114.09~741.35). The results of the Logistic regression analysis showed that gender (OR=1.27, 95%CI=1.02~1.58, P<0.05), age (65~80 years: OR=2.20, 95%CI=1.61~2.99, P<0.001；≥80 years: OR=4.61, 95%CI=2.89~7.34, P<0.001) and multiple medications (<5 prescribed drugs: OR=1.32, 95%CI=1.05~1.66, P<0.05; ≥5 prescribed drugs: OR=12.22, 95%CI=6.83~21.87, P<0.001) were the influencing factors for occurrence of severe ADE associated with avacopan.
Clinicians and pharmacists are advised topay greater attention to severe and new ADE signals not included in drug labeling. They should enhance management and pharmaceutical care for elderly, female, and polypharmacy patients to prevent serious ADE and ensure the patient medication safety.
This article reports the case of a 70-year-old female patient scheduled for surgical intervention due to a space-occupying lesion at the distal common bile duct. The patient presented with severe allergic reactions to plasma-derived human serum albumin (pHSA), precluding its use for correcting hypoalbuminemia. Following informed consent, recombinant human albumin injection (Oryza Sativa) (OsrHSA) was administered as an alternative. The patient received a total of 70 g OsrHSA preoperatively in divided infusions, and her serum albumin level increased from 29.1 g·L-1 to 37.3 g·L-1 without adverse events. She subsequently underwent laparoscopic pancreaticoduodenectomy without complications. OsrHSA was also administered multiple times postoperatively, and no allergic reactions were observed. This case represented the successful application of OsrHSA as a safe alternative to pHSA in perioperative management for complex surgery. To the authors' knowledge, no similar reports have been published to date. This provides a new therapeutic avenue for patients with contraindications to human serum albumin, suggesting that plant-derived recombinant human albumin represents a safe and effective alternative.
To introduce the concepts and tools of risk management in the production process of traditional Chinese medicine preparations.
The differences between the productions of traditional Chinese medicine preparations and chemical drugs were studied. Combined with the characteristics of risk management and control, a match was made. Quality risk management tools such as fishbone diagrams, hazard analysis and critical control points (HACCP), as well as failure mode and effects analysis (FMEA) were used. Taking a certain traditional Chinese medicine preparation production enterprise as an example, quality risk management was carried out on the traditional Chinese medicine preparations it produced.
Through the introduction of the risk management model, the quality control of the entire production process of traditional Chinese medicine preparations has become clearer, enabling the identification of potential hazards in various aspects on a wide scale, thus improving the quality and safety level of traditional Chinese medicine preparations.
The production and quality control of traditional Chinese medicine preparations with the concept and tools of risk management has comparative advantages and is worth popularizing.
Obeticholic acid, a chenodeoxycholic acid derivative among human primary bile acids, acts as an agonist for the farnesoid X receptor. This article introduces a process for the preparation of obeticholic acid and discusses the status of related patent applications concerning its crystalline form. By combining the context of the key patent technology and summarizing related aspects of technology evolution and efficacy relationships, this article aims to provide beneficial references for fair patent placement, patent mining, prevention of patent infringement for imitation businesses, as well as the guidance on technological development and the strategic intellectual property considerations for domestic pharmaceutical businesses.
The purpose of this paper is to investigate the current status of the domestic electronic submission system in relation to the comprehensive lifecycle management of drug registration. We aim to analyze the challenges encountered and propose suggestions for improving China's electronic submission system.
By employing the literature review, this study summarizes and compares the development and current status of the domestic electronic submission system. In light of the actual situation in China, it puts forward targeted suggestions for improvement.
In our country, electronic submisisons are categorized into two forms: electronic common technical document （eCTD） submission and Non-eCTD submission. Currently, we are in a transitional phase where both formats coexist. However, during the implementation process, we still face issues such as non-uniform submission format standards and insufficient capacity of provincial bureaus to receive and review eCTDs. In response to these issues, this paper proposes the following specific measures: ①deepening the reform of eCTD and expanding the implementation range of products. ②Strengthening the effective connection of drug management from market launch to post-market. ③Accelerating the standardization of document submission throughout the entire lifecycle of drugs. Through the implementation of these measures, it is expected to expedite the comprehensive electronic process of drug registration and application in our country, thereby enhancing the efficiency and quality of review and approval.
Since the outbreak of the coronavirus epidemic, how to deal with sudden large-scale infectious diseases has become a global research hotspot. The first mRNA vaccine BNT162b2, which was urgently approved by the US FDA, has shown good efficacy in dealing with the novel coronavirus. It not only provides new solutions for sudden infectious diseases but has also attracted widespread attention in the field of drug research and development. However, the molecular structure of mRNA is unstable, and needs to be delivered to the target site with the support of carriers to exert its efficacy. The composition of mRNA drug delivery carrier is complex and is the main factor causing adverse drug reactions, which may lead to different types of adverse drug reactions, such as immune responses and inflammatory reaction. This paper mainly discusses the potential safety risks in mRNA drug-related carriers, as well as the consideration points and reference cases in non-clinical safety evaluation, so as to provide references for exploring and building scientific safety evaluation methods for mRNA drugs.
To evaluate the safety and tolerance of a single administration versus multiple administrations of recombinant human parathyroid hormone 1-84 (PTH1-84) for injection in Chinese healthy volunteers, as well as to observe the pharmacokinetic characteristics in health individuals following drug administration.
A single center, open, single administration/multiple administration trial was designed. The healthy subjects were divided into four dose groups: 25, 50, 75 and 100 μg, in which the 25 μg dose group was only given at a single dose, and the other three dose groups continued to conduct continuous administration after a single dose. The physical signs of the subjects were recorded, and the biological samples were collected at the time specified in the scheme to calculate and analyze the pharmacokinetic parameters. The safety of different doses of recombinant PTH1-84 was evaluated by the pharmacokinetic parameters of healthy subjects and the occurrence of adverse reactions.
A total of 28 healthy subjects were included in the study, with 4 participants in the 25 μg dosage group and 8 participants in each of the remaining three groups. In the safety evaluation, no correlation between the incidence of adverse events and dosages was observed, and no serious adverse events occurred. The reported adverse reactions resolved favorably. The pharmacokinetic results indicate that recombinant human parathyroid hormone 1-84, within the dosage range of 50 to 100 μg, demonstrates a dose-dependent relationship for both AUC and Cmax following single and multiple administrations. This suggests a positive correlation between drug exposure and dosage.
PTH1-84 has good clinical safety and tolerance at the experimental dose.
To establish and validate a method for determining the plasma concentration of isavuconazole and to apply this method to clinical monitoring of plasma drug concentration.
The plasma samples of isavuconazole were subjected to protein precipitation using methanol. The quantification was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), with stable isotope voriconazole-d4 serving as the internal standard. An Ultimate AQ-C18 chromatographic column was used with a gradient elution of methanol (containing 0.1% formic acid)-water (0.1% formic acid) with a flow rate of 0.3 mL·min-1. The column temperature was set at 40 ℃ and the injection volume of pretreated sample was 5.0 μL. The ion source was positive electrospray ion source, with multiple reaction monitoring mode for positive ion scanning (MRM+). The ion pairs used for quantitative analysis were m/z 438.2→224.1 (isavuconazole) and m/z 354.2→285.1 (voriconazole-d4). After administering a loading dose to five patients, plasma samples were collected on days 4, 5, 6, 12, 13, and 14 post-initiation of treatment to measure the trough concentation of the drug.
The linear range of the isavuconazole detection quality concentration was 0.1~10 μg·mL-1 (r=0.999 6), with a quantification limit of 0.25 μg·mL-1. The within-batch precision and between-run precision were not higher than 11.9%, and the relative errors were between -4.83% and 6.20%. The stability relative errors were between -2.04% and 6.89%. The extraction recoveries rates of isavuconazole and voriconazole-d4, as well as the matrix effects and residual effects, do not influence the quantitative analysis of the analytes. All trough concentrations of the samples from the five patients were within the linear range of the method.
The established LC-MS/MS method for assaying of isavuconazole is simple and accurate. It can be used for the clinical monitoring the plasma concentration of isavuconazole in patients with fungal infections.
To evaluate the effect of Multi-Trace Element Injection (I) on postoperative inflammatory indexes in children with appendicitis.
A total of 68 patients who underwent laparoscopic appendectomy for perforated appendicitis in the Department of General Surgery of Fudan University affiliated pediatric hospital from March 2022 to December 2022 were randomly divided into an experimental group and a control group. The experimental group was given Multi-Trace Element Injection (I) at a dosage of 1 mL·kg-1·d-1 based on routine anti-infection treatment, with a 7-day treatment course. The control group only received routine anti-infection treatment. The inflammatory indexes, abdominal ultrasound and adverse reactions of children in the two groups were compared on the 4th and 7th day post-surgery.
The comparison of CRP value changes between the experimental and control groups 4 days after surgery showed that the experimental group had a baseline change of -85.2（-123，-48.2）, while the control group had a baseline change of -64.0 （-86.2，-26.5）, and the difference was statistically significant (P<0.05). Compared with preoperative levels, the change in PCT 4 days after surgery was -2.30 (-2.50, -2.0) in the experimental group and -0.880 (-2.50, -0.968) in the control group, with a statistically significant difference (P<0.05). The change in WBC count compared to preoperative levels was -7.52 (-10.7, -4.04) in the experimental group and -4.34 (-7.90, -1.19) in the control group, with no statistically significant difference (P>0.05). The comparison of CRP changes between the experimental and control groups 7 days after surgery showed that the experimental group had a baseline change of -125 (-135, -61.2), and the control group had a baseline change of -104 (-149, -76.2), with no statistically significant difference (P>0.05). The change in PCT compared to preoperative levels was -2.79 (-5.41, -1.05) in the experimental group and -1.71 (-4.08, -0.435) in the control group, with no statistically significant difference (P>0.05). The change in WBC count compared to preoperative levels was (-6.63±5.55) in the experimental group and (-6.41±6.64) in the control group, with no statistically significant difference (P>0.05). Covariate analysis showed that after controlling for the status of Multi-Trace Element Injection (I), the experimental group was significantly better than the control group in reducing CRP, PCT and WBC count (P<0.05). This indicates that Multi-Trace Element Injection (I) has a significant effect on reducing inflammation. The effect of the experimental group remained significant under the control of these covariates. There was no statistically significant difference in the incidence of adverse reactions, abdominal ultrasound findings and hospitalization days between the two groups of children (P>0.05).
The application of Multi-Trace Element Injection (I) after laparoscopic appendectomy is safe and effective, and can further reduce postoperative inflammation in children and promote infection improvement.
The medication timing is an important factor affecting the clinical efficacy of drugs. Selecting the right medication timing is the key to ensure the full play of drug efficacy, as well as standardized and precise medication practices in clinical settings. Although some scholars have carried out relevant clinical studies on the medication timing, there remains a lack of systematic review and summary of its important research significance and key points of scheme design. This paper systematically discusses the concept of medication timing, research significance, understanding of traditional Chinese medicine, types of research design and key methodological points, aiming to clarify the design ideas for clinical research on medication timing, and focus on analyzing the similarities and differences, as well as key design points of different types of clinical studies. This article provides methodological guidance for timely and precise medication in clinical practice and effectively promotes the standardization and accuracy of clinical drug use.
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