BMC Pharmacology & Toxicology最新文献

Background: Chronic lymphocytic leukemia (CLL) is a B-cell malignancy primarily diagnosed in older adults. For younger patients, treatment options often include regimens based on fludarabine, cyclophosphamide, and rituximab; however, at least 20% of patients exhibit resistance to these therapies. Ibrutinib, a covalent Bruton's tyrosine kinase (BTK) inhibitor, has demonstrated enhanced safety compared to conventional treatments. This meta-analysis examines the efficacy and safety of ibrutinib in managing relapsed/refractory CLL.

Method: Relevant keywords were used to conduct a comprehensive search across online databases, including PubMed, Scopus, and Google Scholar. Data related to complete response (CR), overall response rate (ORR), and adverse events were extracted to evaluate the efficacy and safety of ibrutinib treatment. The results were presented in forest plots illustrating event rates and risk ratios with 95% confidence intervals (CI), while heterogeneity was assessed using I² statistics. Funnel plots were employed to examine potential publication bias visually.

Result: Twenty-one studies were included in this meta-analysis. Ibrutinib as a single-agent treatment was associated with a 9% complete response (CR) rate (95% CI: 5-14%) and a 77% overall response rate (ORR) (95% CI: 70-83%). When combined with other agents, ibrutinib achieved a CR rate of 21% (95% CI: 9-41%) and an ORR of 84% (95% CI: 80-88%). Adverse events were not significantly correlated with treatment outcomes. Funnel plots indicated no significant publication bias.

Conclusion: Single-agent ibrutinib has proven to be an effective therapy for patients with relapsed/refractory CLL. However, combining ibrutinib with other agents has demonstrated enhanced treatment efficacy. Further studies are needed to evaluate the safety profile of this therapeutic regimen thoroughly.

Background: Deutetrabenazine, a selective vesicular monoamine transporter type 2 (VMAT2) inhibitor, has been demonstrated efficacy in treating refractory neurologic disorders such as Tardive Dyskinesia (TD) and Huntington's disease but have potential adverse events (AEs) that require detailed pharmacovigilance. This study aimed to comprehensively assess the safety profile of deutetrabenazine in real-world settings by analyzing AEs reported from the FDA Adverse Event Reporting System (FAERS) database.

Methods: We conducted a retrospective pharmacovigilance study using FAERS data from Q3 2017 to Q3 2024, focusing on deutetrabenazine-related AEs. We applied four disproportionality analysis methods-Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN) and Multinomial Gamma Poisson Shrinkage (MGPS)--to identify potential safety signals. Furthermore, we utilized the Weibull distribution model to analyze the temporal risk of AEs.

Results: Among the 10,571,578 reports obtained from the FAERS database, 4,337 AE reports were associated with deutetrabenazine. Using four independent computational methods at the preferred term (PT) level, we identified 1,131 PTs that indicated noteworthy adverse reactions. The drug's label-listed adverse reactions, including depression, somnolence, suicidal ideation, and fatigue, showed remarkable signals. Furthermore, we detected potential adverse reactions that were not specified on the label, such as drug ineffectiveness, dyskinesia, death, falls, and insomnia. The majority of these AEs were reported within the initial month of deutetrabenazine treatment, with a median time to onset of 40.5 days.

Conclusion: This research has yielded initial safety insights into the practical use of deutetrabenazine, validating established adverse reactions and uncovering further possible risks. These findings present essential safety considerations for physicians when prescribing deutetrabenazine for the clinical treatment.

Background/objective: Berberine, a naturally occurring alkaloid, has shown promise as a neuroprotective agent in preclinical models of ischemic stroke. This systematic review aims to comprehensively evaluate the neuroprotective effects of berberine in animal models of cerebral ischemia and elucidate its potential mechanisms of action.

Methods: A systematic search was conducted across nine databases, including PubMed, Embase, Cochrane CENTRAL, Web of Science, Scopus, ScienceDirect, Europe PMC, DOAJ, and Google Scholar, from inception to June 30, 2024. Controlled in vivo studies investigating the neuroprotective effects of berberine in animal models of focal cerebral ischemia were included. Two independent reviewers screened studies, extracted data, and assessed the risk of bias using the SYRCLE tool.

Results: Eighteen studies met the inclusion criteria, encompassing various animal models of ischemic stroke. Berberine treatment consistently resulted in significant reductions in infarct volume and improvements in neurological function compared to control groups. Specifically, berberine doses ranging from 10 mg/kg to 300 mg/kg significantly decreased infarct sizes (p < 0.05). Berberine also exhibited anti-inflammatory effects by reducing pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6, and downregulating the TLR4/NF-κB signaling pathway (p < 0.05). Antioxidant effects were evidenced by decreased malondialdehyde levels and increased antioxidant enzymes like superoxide dismutase and glutathione (p < 0.05). Additional findings from studies with smaller sample sizes indicated that berberine reduced apoptotic cell death by decreasing TUNEL-positive cells and modulating apoptosis-related proteins, including increasing Bcl-2 and decreasing cleaved caspase-3 levels (p < 0.05). Berberine also promoted neurogenesis and synaptic plasticity by increasing the expression of BDNF, TrkB, and synaptic proteins SYP and PSD95 (p < 0.05), and enhanced autophagic flux by modulating key autophagy markers (p < 0.05). The risk of bias varied among studies, with some lacking detailed reporting on randomization and blinding procedures.

Conclusion: Berberine demonstrates significant neuroprotective effects in preclinical models of ischemic stroke through multiple mechanisms, including anti-inflammatory, antioxidant, anti-apoptotic, and neuroregenerative actions. These findings support the potential of berberine as a multifaceted therapeutic agent for ischemic stroke. Further well-designed clinical trials are warranted to confirm its efficacy and safety in human patients.

Background: The risk factors for gastrointestinal complications during glucocorticoid therapy in internal medicine inpatients are rarely reported. This study aimed to investigate the risk factors for gastrointestinal complications in internal medicine patients using glucocorticoids.

Methods: Internal medicine inpatients receiving glucocorticoid therapy from February 2023 to September 2023 were included. Gastrointestinal complications were identified by careful review of the electronic medical records of these patients. The risk factors for gastrointestinal complications during glucocorticoid therapy were analyzed by univariable and multivariable logistic regression. Receiver operating characteristic (ROC) curve with Youden's index was used to determine the best cutoff point of the identified continuous variables.

Results: Of the 960 inpatients included, 88 had gastrointestinal complications, with the most common complications including 27 (30.7%) with abdominal discomfort, 26 (29.5%) with acid regurgitation and heartburn, and 14 (15.9%) with asymptomatic positive fecal occult blood. Multiple logistic regression analysis showed that age ≥ 65 years [OR = 2.014, 95% CI (1.096, 3.703), p = 0.024], history of gastroesophageal reflux disease (GERD) [OR = 1.810, 95% CI (1.009, 3.250), p = 0.047], history of peptic ulcer (PU) [OR = 5.636, 95% CI (1.505, 21.102), p = 0.010], maximum dose of glucocorticoids [OR = 1.003, 95% CI (1.001, 1.004), p = 0.001], and nonsteroidal anti-inflammatory drugs (NSAIDs) [OR = 2.788, 95% CI (1.023, 7.597), p = 0.045] were associated with more gastrointestinal complications during glucocorticoid therapy in internal medicine inpatients. ROC curve analysis revealed that when the maximum dose of glucocorticoids was greater than 160 mg, gastrointestinal complications were more likely to occur.

Conclusions: The study shows that age ≥ 65 years, history of GERD, history of PU, maximum dose of glucocorticoids, and NSAIDs are associated with more gastrointestinal complications during glucocorticoid therapy in internal medicine inpatients. Multidisciplinary teams, including physicians, pharmacists, and nurses, should consider increased monitoring to inpatients with high-risk factors.

Objects: The olanzapine/samidorphan (OLZ/SAM) combination is being regarded as a new strategy to combat weight gain induced by olanzapine (OLZ), and its safety is of significant concern. Specifically, as samidorphan is an opioid receptor-related drug, issues related to its potential for dependence and withdrawal symptoms deserve attention. This study aims to provide a comprehensive analysis of adverse events (AEs) associated with the OLZ/SAM.

Methods: This study is a pharmacovigilance study based on the analysis of reports from the FDA Adverse Event Reporting System (FAERS) utilizing the Openvigil online analysis platform for the period from January 1, 2023, to June 30, 2024. Signal results were reported as Reporting Odds Ratios (ROR) along with 95% confidence intervals. A binary logistic regression model was used to analyze the association between the OLZ/SAM and specific AEs.

Results: This study included 86 reports of AEs associated with the OLZ/SAM and 4,678 reports related to OLZ. In terms of frequency of OLZ/SAM-related AEs, off-label use (N = 12) and drug withdrawal syndrome (N = 11) were reported most frequently. Among various system organ classes, the highest frequency of AEs was observed in neurological disorders (SOC) (N = 23). We identified 15 signals associated with the OLZ/SAM. The results of the stepwise regression analysis indicated that in all models, the OLZ/SAM was significantly associated with drug withdrawal syndrome when compared to OLZ (p < 0.01).

Conclusion: The long-term safety of the OLZ/SAM warrants attention, particularly concerning drug withdrawal syndrome.

Background: Methylphenidate, atomoxetine, and amphetamine are the most commonly prescribed medications for ADHD, approved by the FDA. Despite their widespread use, real-world studies on their serious adverse effects are limited. This study leverages the FAERS database to analyze the safety of these drugs.

Methods: A retrospective analysis was conducted using FAERS data from 2004 to 2023. Adverse event (AE) signals for methylphenidate, atomoxetine, and amphetamine were identified by calculating reporting odds ratios (RORs), proportional reporting ratios (PRRs), information components (ICs), and empirical Bayesian geometric mean (EBGM).

Results: The analysis included 72,298 reports, with 37,471 linked to methylphenidate, 17,335 to atomoxetine, and 17,492 to amphetamine. Significant AE signals were found, especially in psychotic disorders for methylphenidate (ROR = 4.47, PRR = 3.7) and amphetamines (ROR = 4.06, PRR = 3.43), and psychiatric and reproductive disorders for atomoxetine (ROR = 5.44, PRR = 4.29; ROR = 2.49, PRR = 2.46). At the PT level, the most common adverse safety signals for the three ADHD drugs were Application site erythema, Somnolence, and Headache. Further analysis showed that "Aggression", "Mydriasis", "Trichotillomania" and suicide-related adverse reactions showed strong signals in the three ADHD drugs. However, there are also differences between the three ADHD medications. For example, serious adverse effects related to cardiovascular and neurological effects were stronger in amphetamines, with the "coronary artery dissection" and "carotid artery dissection" signals being the most significant; "Precocious puberty" has a stronger signal in methylphenidate, and the signal associated with elevated liver enzymes is strongest in atomoxetine. In addition, we also found some PTs that were not included in the drug label, such as "Disturbance in social behaviour" and "Trichotillomania".

Conclusions: In this study, pharmacovigilance analysis of methylphenidate, atomoxetine, and amphetamine was performed using the FAERS database, and we identified significant safety signals. Of note, three ADHD medications are associated with suicide-related signals, amphetamine associated with coronary artery dissection, methylphenidate associated with precocious puberty, and atomoxetine associated with testicle, penile lesions, and liver damage, which require special attention. This study provides a reference for the clinical personalized medication of ADHD patients.

Introduction: Cilostazol has been widely used to prevent peripheral vascular events after PCI. However, guidelines in cilostazol-based triple antiplatelet therapy for patients with ischemic heart disease undergoing PCI remain unclear. The purpose of this study was to assess the efficacy and safety of DAPT (aspirin and clopidogrel) compared to cilostazol -based TAPT (aspirin, clopidogrel and cilostazol).

Methods: We conducted a comprehensive search of the Medline, Embase, Scopus, Cochrane, and Web of Science databases until November 2024 to identify RCTs comparing DAPT with cilostazol -based TAPT in patients with ischemic heart disease undergoing PCI. Pooled risk ratios (RRs) with 95% CIs were calculated.

Results: Eight RCTs (5,299 patients) were included in this systematic review and meta-analysis. A significantly reduced risk of all-cause mortality in hospital was observed with DAPT compared to cilostazol -based TAPT (RR: 0.27, 95% CI: 0.07 to 0.94, p = 0.04). Also, A significantly reduced risk of headache and palpitation was observed with DAPT compared to cilostazol -based TAPT, with pooled RR (RR: 0.15, 95% CI: 0.06 to 0.33, p < 0.001) and (RR: 0.24, 95% CI: 0.08 to 0.73, p = 0.01), respectively. However, no difference was observed between DAPT and cilostazol -based TAPT on vessel revascularization, stroke, stent thrombosis, myocardial infarction and major adverse cardiac events.

Conclusion: Aspirin and clopidogrel were associated with a lower risk of adverse events compared to cilostazol-based TAPT. However, the addition of cilostazol did not improve clinical outcomes. Further trials are needed to clarify the role of cilostazol -based TAPT for patients with ischemic heart disease undergoing PCI.

This study investigates the efficacy of monobenazone, a novel topical agent, in treating psoriasis-like lesions in an imiquimod (IMQ)-induced murine model. Female BALB/c mice were allocated to four groups: negative control, IMQ-treated positive control, monobenazone treatment, and clobetasol propionate treatment. The Psoriasis Area and Severity Index (PASI), histopathological analysis, and cytokine quantification (TNF-α and IL-6) were used to assess treatment outcomes. Monobenazone significantly reduced PASI scores and ameliorated histopathological features, including acanthosis and dermal inflammation, compared to the positive control. Furthermore, monobenazone treatment resulted in decreased levels of pro-inflammatory cytokines TNF-α and IL-6. These findings suggest that monobenazone exhibits therapeutic potential in mitigating psoriasis-like symptoms, potentially through modulation of inflammatory responses. While promising, further research is necessary to elucidate its mechanism of action and clinical applicability as a novel psoriasis treatment.

Background: To assess the food effects and pharmacokinetic profile of oral prednisone (test preparation,5 mg) and prednisolone tablets (reference preparation,5 mg) using a randomized, two-period, two crossover, single-dose, fast and fed trial in 48 (24 in fast, 24 in fed) healthy Chinese adult subjects.

Materials and methods: In the trial, the plasma concentrations were determined at different time points up to 24 h and the pharmacokinetic parameters were analyzed according to the concentration data by non-compartmental analysis using WinNonlin software. All laboratory parameters, vital signs and adverse events (AEs) were monitored and recorded under the supervision of the clinicians throughout the whole process of the study.

Results: Prednisone and prednisolone undergo interconversion in liver. On average, the bioavailability of prednisolone after oral prednisone is approximately 80% of that after prednisolone. And about 20% of prednisolone is converted to prednisone after administration of equivalent oral of prednisolone tablet. Food taken with prednisone or prednisolone tablets delays the time reach the peak prednisone or prednisolone concentration (T_max) by approximately 0.5 h but does not affect systemic exposure. Prednisone and prednisolone tablets were well tolerated, and there were no serious adverse events reported in the study.

Conclusions: For there was no information about the pharmacokinetic profile and food effects of oral prednisone and prednisolone tablets, the result of this research would be a clinical medication for doctors especially dealing patients with varying degrees of liver diseases.

Clinical trial registration: CTR20200093; registered in http://www.chinadrugtrials.org.cn/ at 11 March 2020.