BMC Pharmacology & Toxicology最新文献

Background: Our study aimed to assess the risk signals of antibiotic-associated diarrhea (AAD) caused by various antibiotics using real-world data and provide references for safe clinical applications.

Methods: We analyzed data extracted from the FDA Adverse Event Reporting System (FAERS) database, covering the period from the first quarter of 2004 to the third quarter of 2022. We computed the reporting odds ratio (ROR) for each antibiotic or antibiotic class to compare the signal difference. Furthermore, we also examined the differences in the onset times and outcomes of AAD caused by various antibiotics.

Results: A total of 5,397 reports met the inclusion requirements. Almost all antibiotics, except tobramycin and minocycline (ROR 0.98; 95%CI: 0.64-1.51 and 0.42; 95%CI: 0.16-1.11, respectively), showed a significant correlation with AAD. The analysis of the correlation between different classes of antibiotics and AAD revealed that lincomycins (ROR 29.19; 95%CI: 27.06-31.50), third-generation cephalosporins (ROR 15.96; 95%CI: 14.58-17.47), and first/second generation cephalosporins (ROR 15.29; 95%CI: 13.74-17.01) ranked the top three. The ROR values for antibiotics from the same class of antibiotics also varied greatly, with the ROR values for third-generation cephalosporins ranging from 9.97 to 58.59. There were also differences in ROR values between β-lactamase inhibitors and their corresponding β-lactamase drugs, such as amoxicillin-clavulanate (ROR = 13.31; 95%CI: 12.09-14.65) and amoxicillin (ROR = 6.50; 95%CI: 5.69-7.44). 91.35% of antibiotics have an onset time of less than four weeks.

Conclusions: There is a significant correlation between almost all antibiotics and AAD, particularly lincomycins and β-lactam antibiotics, as well as a different correlation within the same class. These findings offer valuable evidence for selecting antibiotics appropriately.

Objective: The main purpose was to evaluate the efficacy and tolerability of different medications used to treat bulimia nervosa (BN).

Methods: Randomized controlled trials (RCTs) were identified from published sources through searches in PubMed, Cochrane Library, Web of Science, and Embase from inception to November 2022. Primary outcomes were changes in the frequency of binge eating episodes and vomiting episodes from baseline to endpoint. Secondary outcomes were differences in the improvement of scores in depressive symptoms, tolerability (dropout due to adverse events) and weight change.

Results: The literature search ultimately included 11 drugs, 33 studies and 6 types of drugs, 8 trials with TCAs (imipramine, desipramine), 14 with SSRIs (fluoxetine, citalopram and fluvoxamine), 6 with MAOIs (phenelzine, moclobemide and brofaromine), 3 with antiepileptic drugs (topiramate), 1 with mood stabilizers (lithium), and 1 with amphetamine-type appetite suppressant (fenfluramine). The reduction in binge eating episodes was more likely due to these drugs than the placebo, and the SMD was -0.4 (95% CI -0.61 ~ -0.19); the changes in the frequency of vomiting episodes (SMD = -0.16, 95% CI -0.3 ~ -0.03); weight (WMD = -3.05, 95% CI -5.97 ~ -0.13); and depressive symptoms (SMD = -0.32, 95% CI -0.51 ~ -0.13). However, no significant difference was found in dropout due to adverse events (RR = 1.66, 95% CI 1.14 ~ 2.41).

Conclusions: This meta-analysis indicates that most pharmacotherapies decreased the frequency of binge-eating and vomiting episodes, body weight, and depressive symptoms in BN patients, but the efficacy was not significant. In each drug the efficacy is different, treating different aspects, different symptoms to improve the clinical performance of bulimia nervosa.

Objective: To evaluate the efficacy and safety of thrombopoietin receptor agonists (TPO-RAs) in solid tumors with chemotherapy-induced thrombocytopenia (CIT).

Methods: We conducted a comprehensive search of PubMed, FMRS, Cochrane Library, Web of Science, EMBASE, and ClinicalTrials.gov for randomized controlled trials (RCTs) reporting the efficacy and safety of TPO-RAs in solid tumors with CIT. The search was limited to articles published before April 30, 2022. Primary outcomes included chemotherapy dose reduction or delays, platelet transfusion, the incidence of grade 3 or 4 thrombocytopenia, and bleeding events. Secondary outcomes encompassed the incidence of platelet count > 400 × 10⁹/L, adverse events (AEs), serious AEs, thrombosis, and mortality.

Results: Our analysis encompassed six studies: five rigorous RCTs and one unique study comparing romiplostim to an observation group, involving a total of 489 patients. For primary outcomes, TPO-RAs significantly reduced the incidence of grade 3 or 4 thrombocytopenia (RR = 0.69, 95% CI: 0.52-0.91). After applying the Bonferroni correction for multiple comparisons, the significance of the reduction in grade 3 or 4 thrombocytopenia incidence persisted (P = 0.008). TPO-RAs showed no significant impact on chemotherapy dose reduction or delays (RR = 0.81, 95% CI: 0.65-1.01), platelet transfusion (RR = 1.04, 95% CI: 0.48-2.27), or bleeding events (RR = 0.50, 95% CI: 0.23-1.10). In terms of safety, there were no significant difference in the incidence of any AEs (RR = 0.98, 95% CI:0.92-1.04), serious AEs (RR = 0.79, 95% CI:0.45-1.40), thrombotic events (RR = 1.20, 95% CI:0.51-2.84) and mortality (RR = 1.15, 95% CI:0.55-2.41).

Conclusions: This meta-analysis suggests that TPO-RAs are generally well-tolerated. However, their efficacy in solid tumors with CIT appears limited, as they only demonstrate a reduction in the incidence of grade 3 or 4 thrombocytopenia.

Background: Nebulizers are commonly used to treat respiratory diseases, which are a major cause of morbidity and mortality. While inhalation therapy with antibodies has been evaluated in preclinical studies and clinical trials for respiratory diseases, it has not yet been approved for treatment. Moreover, there is limited information regarding the delivery efficiency of therapeutic antibodies via nebulizer.

Methods: In this study, the nebulization characteristics and drug delivery efficiencies were compared when immunoglobulin G (IgG) was delivered by five nebulizers using two airway models and five breathing patterns. The study confirmed that the delivered dose and drug delivery efficiency were reduced in the child model compared to those in the adult model and in the asthma pattern compared to those in the normal breathing pattern.

Results: The NE-SM1 NEPLUS vibrating mesh nebulizer demonstrated the highest delivery efficiency when calculated as a percentage of the loading dose, whereas the PARI BOY SX + LC SPRINT (breath-enhanced) jet nebulizer had the highest delivery efficiency when calculated as a percentage of the emitted dose.

Conclusion: The results suggest that the total inspiration volume, output rate, and particle size should be considered when IgG nebulization is used. We, therefore, propose a method for evaluating the efficiency of nebulizer for predicting antibody drug delivery.

The prediction of intestinal absorption of various drugs based on computer simulations has been a reality. However, in vivo pharmacokinetic simulations and virtual bioequivalence evaluation based on GastroPlus™ have not been found. This study aimed to simulate plasma concentrations with different dissolution profiles and run population simulations to evaluate the bioequivalence of test and reference products of atorvastation using GastroPlus software. The dissolution profiles of the reference and test products of atorvastatin (20 mg tablets), and clinical plasma concentration-time data of the reference product were used for the simulations. The results showed that the simulated models were successfully established for atorvastatin tablets. Population simulation results indicated that the test formulation was bioequivalent to the reference formulation. The findings suggest that modelling is an essential tool to demonstrating the possibility of pharmacokinetic and bioequivalence for atorvastatin. It will contribute to understanding the potential risks during the development of generic products.

Background: Imidacloprid is a neonicotinoid insecticide belonging to the chloronicotinyl nitroguanidine chemical family. Toxicity of IMD for mammals in scientific studies has shown high mutagenic, immunotoxic, teratogenic and neurotoxic effects. The present study was designed to assess the toxic effects of imidacloprid (IMD) on the testicular and epididymis tissues as well as testosterone levels of neonatal male rats.

Methods: Neonatal male rats from postnatal day (PND) 1 to PND 26 were consecutively administered with different concentrations of IMD (1, 5 and 10 mg/kg) subcutaneously. The effect of IMD on body and organ weight, lipid profile, histopathological alterations, oxidative stress and altered testosterone levels were assessed in the testis and plasma.

Results: The results of body weight gain showed a significant difference in group 4 (10 mg/kg) animals as compared to the control. A significant increase in total cholesterol and triglycerides, while a decrease in high-density lipoprotein concentrations was evident. Similarly, a significant decrease in concentrations of antioxidant enzymes (CAT and SOD) among all the IMD-treated groups was evident, when compared to the control. Increased production of ROS was also noticed in the highest-dose treatment group. Further, we observed that IMD-treated rats indicated histopathological changes in the testis and epididymis along with a significant decrease in the plasma testosterone concentrations among IMI-treated groups in contrast to the control. Histological examination of the testis of IMD-treated neonatal male rats also showed decreased spermatogenesis in the treated groups when compared to the control. Furthermore, an increase in lumen diameter and a decrease in epithelial height of seminiferous tubules were also observed in IMD-treated rats in comparison with the control.

Conclusion: It is concluded that sub-chronic exposure to IMD in neonatal male rats may induce histopathological changes in reproductive tissues and damage normal testicular functions via inducing oxidative stress, decrease in body weight, disturbing normal blood lipid profile and testosterone concentration. IMD exposure can induce pathophysiological effects calls for further evaluation of this widely used insecticide.

Background: Atherosclerosis is a form of cardiovascular disease that affects the endothelium of the blood vessel. Series of events are involved in the pathophysiology of this disease which includes the breaking down of the connective tissue elastin and collagen responsible for the tensile strength of the arterial wall by proteolytic enzyme. One of these enzymes called Cathepsin S (CatS) is upregulated in the progression of the disease and its inhibition has been proposed to be a promising pharmacological target to improve the prognosis of the disease condition. Asiatic acid and asiaticoside A are both pentacyclic triterpenoids isolated from Centella asiatica. Their use in treating various cardiovascular diseases has been reported.

Methods: In this study through in silico and in vitro methods, the pharmacokinetic properties, residue interaction, and inhibitory activities of these compounds were checked against the CatS enzyme. The SwissADME online package and the ToxTree 3.01 version of the offline software were used to determine the physicochemical properties of the compounds.

Result: Asiatic acid reported no violation of the Lipinski rule while asiaticoside A violated the rule with regards to its molecular structure and size. The molecular docking was done using Molecular Operating Environment (MOE) and the S-score of - 7.25988, - 7.08466, and - 4.147913 Kcal/mol were recorded for LY300328, asiaticoside A, and asiatic acid respectively. Asiaticoside A has a docking score value (- 7.08466Kcal/mol) close to the co-crystallize compound. Apart from the close docking score, the amino acid residue glycine69 and asparagine163 both interact with the co-crystallized compound and asiaticoside A. The in vitro result clearly shows the inhibitory effect of asiaticoside and asiatic acid. Asiaticoside A has an inhibitory value of about 40% and asiatic acid has an inhibitory value of about 20%.

Conclusion: This clearly shows that asiaticoside will be a better drug candidate than asiatic acid in inhibiting the CatS enzyme for the purpose of improving the outcome of atherosclerosis. However, certain modifications need to be made to the structural make-up of asiaticoside A to improve its pharmacokinetics properties.

Background: The study was designed to investigate effects of single intravenous injection of esketamine on the incidence of postpartum depression (PPD) after labor analgesia and explore the potential mechanisms.

Methods: A total of 120 women who underwent labor analgesia by epidural analgesia pump were enrolled and divided into two groups randomly. Esketamine at a dose of 0.2 mg/kg was intravenously injected after fetal disengagement in the test group and placebo was administered in the control group. The occurrence of PPD and side effects after delivery were recorded. Some indicators related to stress and inflammation were measured before labor analgesia and at 24 h, 1 week, and 6 weeks after delivery in this study. Data were analyzed by independent t-test, repeated measures analysis of variance and Chi-square test in SPSS software (version 25.0). It was considered statistically significant since a p value less than 0.05.

Results: The incidence of PPD was significantly decreased both for one week and six weeks after delivery by using of esketamine (3.4% vs. 15.3%, p = 0.004 and 5.2% vs. 18.6%, p = 0.006, respectively). There were also significant differences between the stress and inflammation-related indicators in different time points in this study, while the side effects for 48 h after delivery were similar between the two groups.

Conclusions: Single intravenous injection of esketamine after delivery in participants underwent labor analgesia can decrease the occurrence of postpartum depression for one week and six weeks after delivery, while the side effects were not increased. The antidepressant effects of esketamine may be related to the reduction of stress response and inflammation.

Trial registration: The trial was registered at the Chinese Clinical Trial Registry on 5/30/2022 (CTRI registration number-ChiCTR2200060387). URL of registry: https://www.chictr.org.cn/bin/home .

Purpose: Dyslipidemia, characterized by elevated levels of triglycerides (TG), low-density lipoprotein (LDL), total cholesterol (TC), and reduced levels of high-density lipoprotein (HDL), is a major risk factor for cardiovascular diseases (CVD). Several studies have shown the potential of acarbose in improving serum lipid markers. However, there have been conflicting results on the topic in adults. Therefore, a comprehensive systematic review and meta-analysis was conducted to assess the impact of acarbose on lipid profiles.

Methods: The random-effects approach was used to combine the data, and the results were provided as weighted mean difference (WMD) with 95% confidence intervals (CI).

Results: Our meta-analysis included a total of 74 studies with a combined sample size of 7046 participants. The results of the analysis showed that acarbose resulted in a reduction in levels of TG (WMD = - 13.43 mg/dl, 95% CI: - 19.20, - 7.67; P < 0.001) and TC (WMD = - 1.93 mg/dl, 95% CI: - 3.71, - 0.15; P = 0.033), but did not affect other lipid markers. When conducting a nonlinear dose-response analysis, we found that acarbose was associated with an increase in levels of HDL (coefficients = 0.50, P = 0.012), with the highest increase observed at a dosage of 400 mg/d. Furthermore, our findings suggested a non-linear relationship between the duration of the intervention and TC (coefficients = - 18.00, P = 0.032), with a decline observed after 50 weeks of treatment.

Conclusion: The findings of this study suggest that acarbose can reduce serum levels of TG and TC. However, no significant effects were observed on LDL or HDL levels.

Objective: Adverse drug reactions (ADRs) caused by opioid drugs show individual differences. Our objective was to explore the association between gene polymorphism and ADRs induced by opioid drugs.

Methods: Evidence-based medical data analysis was conducted for genes related to ADRs induced by opioid drugs to select target genes. Sixty patients with cancer pain who had ADRs after taking opioid drugs (morphine, codeine, oxycodone) and 60 patients without ADRs after taking opioid drugs were used as the experimental group and control group, respectively. Then, we used polymerase chain reaction (PCR) or in situ hybridization to detect target genes. By combining with clinical data such as age, sex, dosage and duration of medication, the effect of gene polymorphism on the ADR of patients after taking opioid drugs was statistically analysed.

Results: Based on a database search and evidence-based medical data, we identified CYP2D6*10, CYP3A5*3, ABCB1, and OPRM1 as target genes for detection. The results of statistical analysis showed no significant difference in genotype distribution between the experimental group and the control group (p > 0.05). However, if 32 patients with ADRs after taking oxycodone and 32 controls were selected for comparison, the SPSS22.0 and SNPStats genetic models showed that the ABCB1 (062rs1045642) CT and TT genotypes correlated with the occurrence of ADRs (p < 0.05): the total number of CT + TT genotypes in the experimental group was 29 (90.62%), with 11 (34.37%) CT + TT genotypes types in the control group.

Conclusion: Polymorphism of ABCB1 (062rs1045642) is related to ADRs caused by oxycodone, and the incidence of ADRs is higher with the allele T. Polymorphism of ABCB1 is expected to become a clinical predictor of ADRs to oxycodone, and attention should be given to the occurrence of serious ADRs in patients with ABCB1 (062rs1045642) CT and TT genotypes.