International Journal Of Clinical Pharmacology And Therapeutics[JOURNAL]
Sun
200 papers
Alleviation of renal ischemia-reperfusion injury by quercetin, kaempferol, and luteolin in Shiwei Hezi pill (SHP): Network pharmacology and molecular docking analysis of a traditional Tibetan herbal agent.
Gomchok D, Yang H, Wuren T
Int J Clin Pharmacol Ther · 2025 Jun · PMID 40035402 · Publisher ↗
OBJECTIVE: The aim of the study was to utilize a systematic network pharmacology approach to explore the active components, targets, and pathways associated with the efficacy of Shiwei Hezi pill (SHP) in treating renal i...
OBJECTIVE: The aim of the study was to utilize a systematic network pharmacology approach to explore the active components, targets, and pathways associated with the efficacy of Shiwei Hezi pill (SHP) in treating renal ischemia-reperfusion injury (RIRI). MATERIALS AND METHODS: We utilized online databases to identify common targets of SHP and RIRI. Functional annotation of genes using the Gene Ontology (GO) and enrichment analysis of pathways using the Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed using bioinformatics websites. Cytoscape was utilized to generate and visualize protein-protein interaction (PPI) networks. We employed specialist software to conduct molecular docking analysis on crucial constituents and targets in order to validate the interaction patterns between core ingredients and essential targets. RESULTS: We screened 54 ingredients with good bioavailability in SHP and identified 204 shared targets between SHP and RIRI. Our data suggests that SHP may primarily target TNF, IL6, GAPDH, MMP9, PTGS2, and MMP6 in the therapeutic management of RIRI. The GO enrichment and KEGG pathway enrichment show that the mechanism of SHP treatment for RIRI involves multiple biological processes and signaling pathways. The molecular docking indicates that the three most potent active components of SHP (quercetin, kaempferol, and luteolin) have a strong likelihood of binding to TNF, IL6, GAPDH, MMP9, and PTGS2 with a high degree of affinity. CONCLUSION: This is the first exploration of the potential mechanism of Tibetan medicine formula SHP in treating RIRI using network pharmacology. Our research indicates that the various components of SHP could act on multiple targets and signaling pathways associated with RIRI. The findings in this study provide a theoretical basis and a novel method for the clinical therapy of RIRI.
Differentiation of bone marrow mesenchymal stem cells modulated by Bushen Tian Sui decoction via the TGF-β1-Smad2/3 signaling pathway: In vitro evidence and potential clinical application in delayed fracture healing.
Xiong W, Li B, Chen J … +5 more , Shao Z, Sun WK, Li S, Lu H, Cheng L
Int J Clin Pharmacol Ther · 2025 May · PMID 40013965 · Publisher ↗
BACKGROUND: Bone-related disorders pose significant challenges in clinical practice. Bone marrow mesenchymal stem cells (BMSCs), as multipotent stem cells, play a pivotal role in bone regeneration. The TGF-β1-Smad2/3 sig...
BACKGROUND: Bone-related disorders pose significant challenges in clinical practice. Bone marrow mesenchymal stem cells (BMSCs), as multipotent stem cells, play a pivotal role in bone regeneration. The TGF-β1-Smad2/3 signaling pathway is a well-recognized regulator of BMSC osteogenic differentiation. Traditional Chinese medicine (TCM), such as Bushen Tian Sui decoction (BSTSD), has shown potential in enhancing bone health; however, its molecular mechanisms remain poorly understood. OBJECTIVE: Investigating the effects and underlying mechanisms of BSTSD on the osteogenic differentiation of BMSCs. MATERIALS AND METHODS: The impact of BSTSD on BMSCs was comprehensively analyzed using Cell Counting Kit-8 (CCK8), quantitative polymerase chain reaction (qPCR), western blot (WB), and immunofluorescence assays. RESULTS: CCK8 results revealed the highest optical density (OD) values in the BSTSD + activator group at 24, 48, and 72 hours, indicating enhanced cell proliferation. qPCR analysis showed significantly increased expression levels of TGF-β1, Smad2, Smad3, SOX9, and RUNX2 in the BSTSD + activator group, suggesting a synergistic effect in promoting osteogenic and chondrogenic differentiation. WB results demonstrated elevated phosphorylation levels of Smad2 and Smad3 (p-Smad2, p-Smad3) in the BSTSD + activator group, while total Smad2 and Smad3 protein levels remained consistent among groups. Immunofluorescence assays confirmed the highest fluorescence intensity, positive area ratio, and cell count containing Smad2 and Smad3 proteins in the BSTSD + activator group, validating the synergistic effect of BSTSD and TGF-β1. CONCLUSION: BSTSD exhibits promising effects on BMSC differentiation and bone regeneration, mediated through the TGF-β1-Smad2/3 signaling pathway.
Bisphosphonates in combination with alendronate sodium increase bone mineral density and modulate IL-6, TNF-α, and IGF-1 in patients with osteoporosis.
Gu X, Zhang L, Chen X … +1 more , Kong L
Int J Clin Pharmacol Ther · 2025 Apr · PMID 40013964 · Publisher ↗
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...
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.
Evidence for a loss of analgesia when hydromorphone is administered in combination with hange-shashin-to: Enterohepatic circulation and β-glucuronidase inhibition.
Ozaki M, Yamagata H, Matsui H … +4 more , Okada N, Matsumoto M, Nagano H, Kitahara T
Int J Clin Pharmacol Ther · 2025 Apr · PMID 40013963 · Publisher ↗
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Network pharmacology and experimental analysis of Yudantong decoction, a multi-immunomodulator for the treatment of intractable cholestatic liver disease: Identification of active agents, molecular targets, and mechanisms of action.
Wu X, Hou L, Liu J … +4 more , Hao J, Liu C, Hu Y, He Q
Int J Clin Pharmacol Ther · 2025 May · PMID 40013962 · Publisher ↗
BACKGROUND: Yudantong decoction (YDTD) is a therapeutic prescription for cholestatic liver disease (CLD) and is clinically effective in our medical institution. However, the exact constituents and mechanisms of YDTD in t...
BACKGROUND: Yudantong decoction (YDTD) is a therapeutic prescription for cholestatic liver disease (CLD) and is clinically effective in our medical institution. However, the exact constituents and mechanisms of YDTD in treating CLD remain unknown. This project aimed to explore the primary constituents and mechanism of YDTD in the treatment of CLD through ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS), network pharmacology, molecular docking technology, and in vivo experiments. MATERIALS AND METHODS: The chemical constituents of YDTD were identified via UPLC-HRMS, and Bioinformatics analysis tool for molecular mechANism of traditional Chinese medicine (BATMAN-TCM) was employed to screen target proteins. Cytoscape 3.7.1 was used to build the herbal component-target network. The CLD targets were identified by querying the OMIM and DisGeNET databases and determining the overlap between the targets of the YDTD chemical constituents and those of CLD. The STRING database was utilized to construct a protein-protein interaction (PPI) network for subsequent analysis. Gene ontology (GO) biological process enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis were carried out using the database for annotation, visualization and integrated discovery (DAVID) database. Molecular docking validation against core targets with PyMOL software was conducted for the active compounds. Finally, in vivo experiments were performed to investigate the therapeutic effect of YDTD in a murine model of α-naphthyl isothiocyanate (ANIT)-induced CLD. RESULTS: YDTD has 112 major components, among which 59 have 1,478 potential targets. We identified a total of 1,957 potential therapeutic targets for CLD and 269 overlapping targets between CLD-associated targets and YDTD active component targets to construct a PPI network. Through topology analysis, IL-6, INS, IL1B, AKT1, BCL2, NFKB1, PTGS2, and TP53 were identified as key targets along with their corresponding primary chemical components. KEGG analysis revealed significant enrichment of the phosphoinositide 3-Kinase (PI3K)-Akt and nuclear factor Kappa-B (NF-κB) signaling pathways. The molecular docking results indicated strong binding affinities between glycyrrhizin-AKT1, l-arginine-IL1B, p-coumaric acid-IL1B, 2,4-dihydroxybenzoic acid-IL1B, p-coumaric acid-TNF, 2-hydroxycinnamic acid-TNF, uridine-AKT1, p-coumaric acid-IL6, and trigonelline-INS. In vivo experiments demonstrated that YDTD downregulated the expression of p-PI3K, p-AKT, p-NF-κB, IL-6, TNF-α, and IL-1β, and reduced immune cell infiltration in the liver to ameliorate liver damage in CLD patients. CONCLUSION: The present study clarified the active components and potential anti-inflammatory mechanism of YDTD in treating CLD, providing a solid foundation for future research on its therapeutic mechanisms.
Cardiovascular safety profile of JAK inhibitors and ethnic factors in Asians: A signal detection study using the Global ICSR (WHO-UMC VigBase) database.
Nam W, Bae JH, Oh J … +2 more , Shin JY, Kim H
Int J Clin Pharmacol Ther · 2025 Apr · PMID 40013961 · Publisher ↗
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-...
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.
Niraparib-related severe refractory thrombocytopenia in ovarian cancer patients receiving paclitaxel/carboplatin chemotherapy: A report on three cases.
Chen M, Zhou L, Yang H … +1 more , Wang M
Int J Clin Pharmacol Ther · 2025 Apr · PMID 39928104 · Publisher ↗
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 describ...
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.
Longevity - via traditional Chinese medicine and macrobiotics to AI-driven network pharmacology and clinical pharmacology.
Woodcock-Kloberdanz BG
Int J Clin Pharmacol Ther · 2025 Mar · PMID 39882925 · Publisher ↗
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Valproic acid-induced hyperammonemia with encephalopathy in adults: A meta-analysis.
Huang TK, Su YC, Shih CS
Int J Clin Pharmacol Ther · 2025 Mar · PMID 39873559 · Publisher ↗
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, co...
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.
Sodium-glucose cotransporter-2 inhibitor treatment has differential effects on the incidence of various malignancies: Evidence from a spontaneous adverse reaction database.
Inose R, Muraki Y
Int J Clin Pharmacol Ther · 2025 Mar · PMID 39841012 · Publisher ↗
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 inhibito...
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.
Treatment of delayed fracture healing with Bushen Tiansui decoction: Analysis of active agents and targets using bioinformatics and network pharmacology analysis.
Wang G, Cheng L, Shao Z … +5 more , Li S, Sun W, Liu J, Xiong W, Li H
Int J Clin Pharmacol Ther · 2025 Mar · PMID 39810723 · Publisher ↗
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...
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.
Renoprotective effects of dulaglutide, a GLP-1 agonist, involving regulation of epithelial-mesenchymal transition in patients with type 2 diabetes and diabetic kidney disease.
Jiang D, Meng F, Chou X … +2 more , Shen J, Liu M
Int J Clin Pharmacol Ther · 2025 Apr · PMID 39790030 · Publisher ↗
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...
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.
Severe genital cutaneous toxicity with sunitinib.
Rodríguez Jorge M, Domínguez Senín L, Cobelas Cartagena SS … +2 more , Sánchez Esperilla M, Bayo Calero J
Int J Clin Pharmacol Ther · 2025 Apr · PMID 39773403 · Publisher ↗
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...
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.
Evidence that anticoagulant use decreases in-hospital deaths in patients with new-onset atrial fibrillation.
Hung CT, Lin YJ, Suk CW … +2 more , Shih WH, Wu MM
Int J Clin Pharmacol Ther · 2025 Mar · PMID 39773402 · Publisher ↗
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 th...
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.
Sarcopenia with muscle wasting in hepatic cancer predicts therapeutic outcome after hepatic artery intervention.
Liao Y
Int J Clin Pharmacol Ther · 2025 Feb · PMID 39744802 · Publisher ↗
OBJECTIVES: We aimed to study sarcopenia for its significance in predicting the effect of hepatic artery intervention (HAI) plus lenvatinib on hepatitis B-related hepatocellular carcinoma (HCC) complicated with diabetes...
OBJECTIVES: We aimed to study sarcopenia for its significance in predicting the effect of hepatic artery intervention (HAI) plus lenvatinib on hepatitis B-related hepatocellular carcinoma (HCC) complicated with diabetes mellitus (DM). MATERIALS AND METHODS: Hepatitis B-related HCC patients complicated with DM (n = 102) visiting during January 2021 and December 2023 were retrospectively selected. Computed tomography was performed to detect the third lumbar vertebra for its muscle cross-sectional area. A non-sarcopenia group (59 cases) plus a sarcopenia group (43 cases, men with a skeletal muscle index ≤ 40.8 cm/m and women with a skeletal muscle index ≤ 34.9 cm/m) were established according to different skeletal muscle indexes. RESULTS: Significant decline in body mass index (BMI) and albumin (ALB) level was observed in the sarcopenia group compared to the non-sarcopenia group (p < 0.05). The sarcopenia group, compared with the non-sarcopenia group, exhibited a significantly reduced objective response rate (53.49 vs. 74.58%) (p < 0.05), while no significant intergroup difference was discovered in the disease control rate (95.35 vs. 91.53%) (p < 0.05). Low BMI, alpha fetoprotein (AFP), low ALB, and pre-chemotherapy sarcopenia all influenced the overall clinical efficacy, as independent influencing factors (p < 0.05). CONCLUSION: Sarcopenia may attenuate the efficacy of HAI plus lenvatinib on hepatitis B-related HCC with DM, and BMI, AFP and ALB are factors affecting the therapeutic effect.
Medication reconciliation in intensive care units of a tertiary hospital in Saudi Arabia: An evaluation of medication discrepancies.
Alatmi SA, Aljawadi M, Almuqbil M … +5 more , Aldakhil S, Alqahtani EM, Almalke RA, Alshammari MM, Alhammad AM
Int J Clin Pharmacol Ther · 2025 Feb · PMID 39744801 · Publisher ↗
BACKGROUND: Patients discharged from intensive care units (ICUs) are at higher risk for medication discrepancies, which can harm patients, increase healthcare costs, and lead to readmission. This study aimed to describe...
BACKGROUND: Patients discharged from intensive care units (ICUs) are at higher risk for medication discrepancies, which can harm patients, increase healthcare costs, and lead to readmission. This study aimed to describe the frequency and types of medication discrepancies among ICU patients upon discharge and identify the factors associated with medication discrepancies. MATERIALS AND METHODS: This retrospective cohort study included patients ≥ 18 years old, admitted to medical or surgical ICUs, and discharged on one or more medications. This study was done at a tertiary university hospital in Riyadh, Saudi Arabia. Data were collected through chart review over a 3-month period in 2018. Medication discrepancy was defined as any difference identified between the documented home medication list and the medication list on ICU discharge without any clearly documented justification. χ, Fisher exact test, and logistic regression were used to analyze the data. RESULTS: Out of 204 screened patients, 121 were included. The mean age was 51 ± 15.7 years, 57 (47.1%) were female, and 91 (75.2%) were admitted to the surgical ICU. The median ICU length of stay was 3 (2 - 7) days. In total, 216 medication discrepancies were identified; only 23 (19%) patients were discharged without any medication discrepancies. The mean medication discrepancies identified per patient were 2 ± 1. The most common type of medication discrepancies identified were no indication of therapy (43.8%), drug omissions (33.7%), and discrepancies in the duration of therapy (11.2%). Mechanically ventilated patients were less likely to have medication discrepancies upon discharge (OR = 0.24, 95% CI = (0.07 - 0.90)). CONCLUSION: This study demonstrated many medication discrepancies among patients discharged from ICUs at KSUMC University Hospital in Riyadh, Saudi Arabia. The lack of a systematic approach to medication reconciliation might contribute to the increased number of medication discrepancies in comparison to multiple studies in different countries exploring the medication discrepancies among ICU patients. Establishing a process that includes pharmacist-driven medication reconciliation is needed.
Antibiotic treatment of ceftriaxone-susceptible Serratia marcescens bacteremia: A multicenter, retrospective cohort study.
Mughrabi A, Maamari J, Phillips T … +6 more , Alabbasi A, Brooks A, Nuriev R, Zenkin L, Jaber BL, Nader C
Int J Clin Pharmacol Ther · 2025 Feb · PMID 39744800 · Publisher ↗
BACKGROUND: has recently been categorized as low-risk for AmpC β-lactamase inducible production, but research on outcomes in bacteremia by antibiotic choice is limited. OBJECTIVES: This study examined the clinical char...
BACKGROUND: has recently been categorized as low-risk for AmpC β-lactamase inducible production, but research on outcomes in bacteremia by antibiotic choice is limited. OBJECTIVES: This study examined the clinical characteristics and outcomes of patients with ceftriaxone-susceptible bacteremia who received AmpC-directed β-lactam therapy vs. narrower spectrum therapies. MATERIALS AND METHODS: Records of hospitalized adults with at least one positive blood culture for , over an 8-year period, across seven hospitals in an integrated health care system, were reviewed. RESULTS: Of the 73 identified patients, 17 (23.3%) received carbapenem-based therapy. More than half of cases were community-acquired, with urological and intravenous drug use being the most common sources. While there was a trend toward lower mortality in carbapenem-treated patients (14.8 vs. 0%; p = 0.10), this was not statistically significant. The composite outcome of clinical failure was also not significant. However, compared to non-carbapenem-treated patients, carbapenem-treated patients had longer treatment duration (13 vs. 15 days; p = 0.02), prolonged hospital stays (5 vs. 11 days; p < 0.001), and higher infection-related readmission rates (17.6 vs. 3.6%; p = 0.04). A subset analysis of the 56 non-carbapenem treated patients found no significant difference in 30-day mortality or clinical failure between cefepime and non-cefepime-containing subgroups. CONCLUSION: Our study found that cefepime- or carbapenem-based therapy may have limited clinical relevance in the treatment of bacteremia when the strains are initially susceptible to ceftriaxone, highlighting the importance of antibiotic stewardship to prevent emergence of multidrug resistant organisms.
Topics in focus 2025 The International Journal of Clinical Pharmacology and Therapeutics.
Woodcock-Kloberdanz BG
Int J Clin Pharmacol Ther · 2025 Jan · PMID 39635732 · Publisher ↗
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Warfarin pharmacokinetics and pharmacodynamics are not affected by concomitant administration of the long-acting GLP-1 receptor agonist polyethylene glycol loxenatide.
Zhou H, Wu G, Lv D … +2 more , Lin M, Shentu J
Int J Clin Pharmacol Ther · 2025 Feb · PMID 39607179 · Publisher ↗
OBJECTIVE: To evaluate potential drug-drug interactions between polyethylene glycol loxenatide (PEX-168) and warfarin. MATERIALS AND METHODS: This was an open-label, single-arm, two-treatment, sequential study. 16 health...
OBJECTIVE: To evaluate potential drug-drug interactions between polyethylene glycol loxenatide (PEX-168) and warfarin. MATERIALS AND METHODS: This was an open-label, single-arm, two-treatment, sequential study. 16 healthy male subjects were administered warfarin (5 mg) alone on day 1 and received PEX-168 subcutaneously 200 µg once a week during days 14 - 42, with warfarin (5 mg) on day 44. Pharmacokinetics of R- and S-warfarin, as well as pharmacodynamics of warfarin, as measured by prothrombin time (PT) and international normalized ratio (INR), were assessed. RESULTS: The geometric mean ratios (GMRs) of area under the curve from time zero to the time of the last quantifiable concentration (AUC) for PEX-168 + warfarin vs. warfarin were 0.950 (90% CI: 0.898, 1.006) for R-warfarin and 0.989 (90% CI: 0.946, 1.033) for S-warfarin. The GMRs of maximum observed plasma concentration (C) values were 0.965 (90% CI: 0.893, 1.043) for R-warfarin and 0.983 (90% CI: 0.899, 1.075) for S-warfarin, both of which were contained in the interval 0.80 - 1.25. PEX-168 had no effect on the area under the effect-time curve from time 0 to 168 hours of INR and PT, as demonstrated by the GMRs of 0.987 (90% CI: 0.974, 1.000) and 0.990 (90% CI: 0.979, 1.002), respectively. CONCLUSION: Concomitant administration of PEX-168 and single-dose warfarin was well tolerated. PEX-168 had no effect on the pharmacokinetics or pharmacodynamics of warfarin.
Immune checkpoint inhibitors: A bibliometric analysis of research trends and hotspots based on the most frequently cited clinical trials (2013 - 2021).
Wang P, Zhao L, Jia L … +1 more , Wang L
Int J Clin Pharmacol Ther · 2025 Jan · PMID 39565079 · Publisher ↗
OBJECTIVE: To quantitatively and qualitatively evaluate research trends and hotspots for immune checkpoint inhibitors (ICIs), according to the most frequently cited clinical trials. BACKGROUND: Numerous clinical trials h...
OBJECTIVE: To quantitatively and qualitatively evaluate research trends and hotspots for immune checkpoint inhibitors (ICIs), according to the most frequently cited clinical trials. BACKGROUND: Numerous clinical trials have been carried out using ICIs for activating anti-tumor immunity in cancer patients. The most frequently cited clinical trials have been used as a database for achieving the objectives of this analysis. MATERIALS AND METHODS: The most frequently cited articles on ICIs meeting the inclusion criteria were extracted from the Web of Science database. Citation report information including annual outputs, most relevant journals, and country of origin together with burst references, keywords, information on co-occurrence, citation networks, and cluster topics were analyzed using standard bibliometric procedures. RESULTS: A total of 112 most frequently cited articles on clinical trials of ICIs were retrieved for the period 2013 to 2021 of which the journal had the highest number of citations. Most studies originated in the U.S., and therefore studies from this country had a determinant effect of the results of the investigation. Burst reference topics included studies on ipilimumab for melanoma, anti-PD-L1 antibody in advanced cancer, anti-PD-1 antibody in cancer, nivolumab combined with ipilimumab or as monotherapy in untreated melanoma, and pembrolizumab for PD-L1 positive non-small-cell lung cancer. Nine clusters were grouped in the citation network. The topic/keywords "cancer", "immunotherapy", "PD-1 blockade", "PD-L1", "expression", "ipilimumab", "nivolumab", "pembrolizumab", and "safety" were the search priorities, whereas "multicenter", "resistance", "adverse events", and "renal-cell carcinoma" were seen as emerging topics in this specific field. CONCLUSION: The bibliometric analysis of the most frequently cited clinical trials with ICIs provided information on the characteristics of the studies evaluated as well as hotpots and trends in evolving immunopharmacotherapy research on ICIs.
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