International journal of clinical pharmacology and therapeutics最新文献

A characteristic toxicity of niraparib is a decrease in blood platelets (PLT), with an incidence of ~ 34% for grades 3 - 4 conditions. However, exceedingly severe cases have been reported infrequently. This paper describes three patients with acute and refractory severe PLT deficiency due to niraparib administration. The symptom characteristics, treatment course, and outcomes have also been analyzed, and the potential for the involvement of immune-related factors is considered. Therefore, it is recommended to comprehensively assess bone marrow hematopoietic function and high-risk variables before administering niraparib, intensify self-management and monitoring of patients, track changes in indicators, and intervene promptly. Additionally, if standard PLT-elevating therapies are ineffective, early full-dose administration of thrombopoietin receptor agonists, preferably avatrombopag, may be beneficial for reversing PLT loss of control.

Objective: This study aimed to detect cardiovascular disease-related signals using Global Individual Case Safety Report data on JAK inhibitors.

Materials and methods: A signal detection study was conducted using the WHO-UMC VigiBase.

Results: This study identified four cardiovascular adverse event signals associated with JAK inhibitors in Asian populations, including pulmonary embolism, deep vein thrombosis, thrombosis, and cerebrovascular accidents.

Conclusion: Analysis of Asian populations revealed a higher risk of thromboembolic events associated with JAK inhibitors than with TNF inhibitors. However, unlike in the Western populations, no myocardial infarction signal was detected in the Asian populations.

Introduction: Sunitinib is an oral drug approved for the treatment of metastatic renal cell carcinoma. Serious cutaneous adverse reactions to sunitinib are rare, and when they occur, discontinuation of the treatment may be needed.

Case report: A 70-year-old male patient was diagnosed with stage IV clear cell renal carcinoma and received treatment with sunitinib. After a second cycle with a 25% dose reduction, the patient was admitted with a diagnosis of grade 3 genital erythema. After ruling out other common causes, sunitinib was considered the cause of genital erythema and was stopped. Treatment with corticosteroids, topical applications, and morphine was started, with resolution after 18 days of evolution.

Discussion: There are only a few published reports that describe erythema and scaling of the genital skin. As in those few cases, for our patient, the first clinical signs appeared on day 28 of sunitinib treatment, and the lesions disappeared after 2 weeks without the use of the drug. Erythema and scaling reappeared when the drug was reintroduced, with greater severity than what was described in some of the other cases, which even included cases for which the lesions did not reappear.

Conclusion: Rare instances of severe and limiting skin toxicity may necessitate treatment suspension and compromise survival, as observed in our case. It is crucial to recognize these skin toxicities and understand their appropriate management strategies to initiate treatment as early as possible, thereby avoiding hospitalizations and enabling the resumption of sunitinib therapy.

Aims: To assess the renoprotective effects of dulaglutide and identify mechanisms of action in patients with type 2 diabetes and diabetic kidney disease (DKD).

Materials and methods: Outpatients/ambulant patients at the Department of Endocrinology, Affiliated Hospital of Xuzhou Medical University between October 2021 and July 2023, with type 2 diabetes and DKD, a urinary albumin-to-creatinine ratio (UACR) ≥ 3 mg/mmol and who were receiving hypoglycemic agents were prescribed dulaglutide at a dose rate of 0.75 - 1.5 mg once weekly (intervention group; n = 70). Patients receiving hypoglycemic agents other than glucagon-like peptide-1 (GLP-1) receptor agonists and who were not prescribed dulaglutide constituted the control group (n = 65). Observations/outcomes: The primary outcome was a change in the UACR and biomarkers of epithelial-mesenchymal transition (EMT) determined after 12 months of intervention treatment. Adverse events (estimates of tolerability and safety) were recorded during treatment and a follow-up period of 12 months.

Results: UACR changes in the intervention group compared to the control group were significantly lower (p < 0.01 at 6 months and p < 0.05 at 12 months). The frequency of gastrointestinal adverse events in the two groups were not significantly different, and there were no significant increases in the number of hypoglycemic events. Dulaglutide significantly increased the epithelial marker E-cadherin and inhibited the mesenchymal marker periostin.

Conclusion: It is concluded that dulaglutide causes significant reductions in urinary albumin and modulates EMT-related proteins thereby ameliorating the decline in kidney function in patients with type 2 diabetes and DKD.

Objective: To assess the effects of bisphosphonates (zoledronic acid injection) plus alendronate sodium on bone mineral density (BMD) and levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and insulin-like growth factor I (IGF-I) in patients with osteoporosis.

Materials and methods: A total of 94 patients recruited from osteoporosis patients hospitalized in the period October 2021 to December 2022 were assigned to either a control group or an observation group using a random number table. The control group was treated with alendronate sodium alone, whereas the observation group received zoledronic acid injection in combination with alendronate sodium administered orally.

Results: Pre-treatment values for BMD, serum levels of IL-6, TNF-α, and IGF-I did not differ between the two groups (p > 0.05). However, post-treatment BMD measured at the femoral neck, in lumbar vertebrae, and Ward's triangle were increased, as was serum IGF-I level (p < 0.05). In contrast, in comparison with the control group, reductions were observed in serum IL-6 and TNF-α (p < 0.05). The incidence of adverse reactions such as nausea and vomiting, diarrhea, musculoskeletal pain, and hypocalcemia was significantly lower in the observation group (p < 0.05).

Conclusion: Zoledronic acid injection in combination with alendronate sodium increases the expression of IL-6, TNF-α, and IGF-I, suppresses bone resorption and promotes bone recovery in patients with osteoporosis.

Objective: This study aims to utilize bioinformatics and network pharmacology to identify the active components of Bushen Tiansui decoction (BSTSD) and elucidate its molecular mechanisms and targets in promoting delayed fracture healing.

Materials and methods: Using various databases and tools, we identified 155 active compounds within BSTSD's herbal components. Key compounds such as eriodictyol and β-sitosterol were noted for their significant anti-inflammatory, antioxidant, and immunomodulatory effects, which are crucial for promoting fracture healing.

Results: Network analysis revealed compounds such as kaempferol and luteolin as having high centrality within the network, indicating their central role in the therapeutic effects of BSTSD. Gene ontology (GO) enrichment analysis highlighted that biological processes such as gland development and aging are vital for fracture healing. Cellular components like membrane rafts and microdomains are essential for maintaining cellular functions and signal transduction during bone repair. Molecular functions such as protein serine/threonine kinase activity play key roles in regulating bone cell proliferation, differentiation, and remodeling. KEGG pathway analysis identified critical pathways including prostate cancer, proteoglycans in cancer, lipid and atherosclerosis, EGFR tyrosine kinase inhibitor resistance, chemical carcinogenesis receptor activation, PI3K-Akt signaling pathway, hepatitis B, endocrine resistance, HIF-1 signaling pathway, and estrogen signaling pathway. Molecular docking results showed strong binding affinities between key compounds and target proteins, supporting the reliability of the network pharmacology predictions.

Conclusion: This study provides a comprehensive understanding of the molecular mechanisms by which BSTSD promotes fracture healing, identifying active compounds and pathways that offer scientific bases for the clinical application of BSTSD and paving the way for further experimental validation and therapeutic development.

Objective: Sodium-glucose cotransporter (SGLT) 2 inhibitors are expected to demonstrate secondary effects against malignancy. However, long-term and large-scale data are required to evaluate the effects of SGLT2 inhibitors on malignancy, which has not been sufficiently studied in clinical practice. This study aimed to evaluate the association between SGLT2 inhibitors and malignancy using the spontaneous adverse reaction database.

Materials and methods: The United States Food and Drug Administration Adverse Event Reporting System database between 1997 (4Q) and 2020 (2Q) was used in this study. Reporting odds ratio (ROR) was selected as the safety-signaling measure. An inverse signal suggesting potential alternative therapeutic opportunities was defined when the upper limit of 95% confidence interval (CI) was < 1. The association between SGLT2 inhibitors and malignancies was evaluated.

Results: The total number of reports in the database during the study period was 13,106,455. SGLT2 inhibitors showed significant associations with pancreatic cancer (ROR: 3.08. 95% CI: 2.68 - 3.55), and kidney cancer (ROR: 1.39. 95% CI: 1.13 - 1.72). SGLT2 inhibitors showed significant inverse associations with breast cancer (ROR: 0.32. 95% CI: 0.27 - 0.39), lung cancer (ROR: 0.47. 95% CI: 0.37 - 0.59), liver cancer (ROR: 0.68. 95% CI: 0.50 - 0.93), and malignant melanoma (ROR: 0.49. 95% CI: 0.34 - 0.70).

Conclusion: SGLT2 inhibitors may increase the incidence of pancreatic cancer and kidney cancer, and decrease the incidence of breast cancer, lung cancer, liver cancer, and malignant melanoma. These associations need to be further examined in other clinical studies and research in the future.

Objective: Current guidelines provide no clear recommendations for managing new-onset atrial fibrillation in critical illness, particularly with respect to anticoagulant use. This retrospective study aimed to evaluate the efficacy and safety of anticoagulants in such patients.

Materials and methods: Patients in the intensive care unit with new-onset atrial fibrillation were recruited during the period January 1, 2021, to June 30, 2022. Ischemic stroke and bleeding were considered primary outcomes, and in-hospital death was considered the secondary outcome. Hazard ratios for outcomes were determined using the Cox proportional hazard model.

Results: A total of 92 patients were included in the study of which 29 were anticoagulant users and 63 non-users. No significant differences were observed on the risk of ischemic stroke (HR, 3.46; 95% CI, 0.22 - 55.8, p = 0.38) and bleeding (HR, 1.07; 95% CI, 0.52 - 2.23, p = 0.85), but anticoagulant use was associated with a significantly decreased risk of in-hospital death (HR, 0.43; 95% CI, 0.19 - 0.97, p = 0.04).

Conclusion: Anticoagulant use in critically ill patients with new-onset atrial fibrillation did not increase the risk of bleeding and ischemic stroke but significantly reduced in-hospital deaths. These findings need confirmation in a randomized controlled trial.

Objective: Valproic acid, frequently prescribed for neurological and psychiatric disorders, can cause hyperammonemia (HA). This retrospective study aimed to investigate the association among the basic characteristics, comorbidities, co-medications, and risk of HA in patients receiving valproic acid.

Materials and methods: We compared groups with and without HA using data collected from the medical records of adults undergoing valproic acid monitoring between January 1, 2019, and December 31, 2021. We conducted a multivariable logistic regression analysis to explore the risk factors for HA and a comprehensive systematic literature review to identify factors significantly associated with valproic acid-related HA.

Results: In total, 247 patients were included, with 37 in the HA group (serum ammonia level > 150 mcg/dL); almost all of them eventually developed hyperammonemic encephalopathy (HE). Multivariable logistic regression analysis revealed that valproic acid levels (odds ratio (OR): 1.01, 95% confidence interval (CI): 0.99 - 1.03), epilepsy (OR: 3.82, 95% CI: 1.52 - 9.62), congestive heart failure (OR: 32.3, 95% CI: 4.09 - 255.4), and concomitant phenytoin use (OR: 6.4, 95% CI: 1.07 - 38.12) are independently associated with HA development during valproic acid therapy. Our data and those of previous studies demonstrate significant associations of valproic acid-related HA with concomitant phenytoin and topiramate use; serum valproic acid concentrations were also significantly positively correlated with serum ammonia levels.

Conclusion: The results suggest that serum ammonia and valproic acid levels should be monitored during valproic acid treatment, particularly with concurrent use of phenytoin or topiramate, to prevent further deterioration of HE.