BMC Pharmacology and Toxicology最新文献

{"title":"Risk of CKD among patients with DM taking diuretics or SGLT2i: a retrospective cohort study in Taiwan","authors":"Han-Jie Lin, Pin-Yang Shih, Stella Chin-Shaw Tsai, Wu-Lung Chuang, Tsai-Ling Hsieh, Heng-Jun Lin, Teng-Shun Yu, Fuu-Jen Tsai, Chiu-Ying Chen, Kuang-Hsi Chang","doi":"10.1186/s40360-024-00745-7","DOIUrl":"https://doi.org/10.1186/s40360-024-00745-7","url":null,"abstract":"This study aimed to evaluate the long-term risk of CKD and renal function declines using a combination of diuretics and SGLT2i. We selected the data of subjects who had at least two outpatient records or at least one inpatient record for DM treatment as the DM group from the National Health Insurance Research Database (NHIRD). Patients receiving versus not receiving SGLT2i were defined as the SGLT2i and non-SGLT2i cohorts, respectively. The patients in the two groups were matched 1:1 through propensity score matching based on age, sex, year of index date, and comorbidities. The diuretics-only group had a higher risk of CKD (aHR, 2.46; 95% CI, 1.68–3.61) compared to the neither SGLT2i nor diuretics group, while the both SGLT2i and diuretics group and the SGLT2i only group had lower risks (aHR, 0.45, 95% CI, 0.32–0.63; aHR, 0.26, 95% CI, 0.17–0.40) than the diuretics-only group. The SGLT2i-only group had a lower risk (aHR, 0.58, 95% CI, 0.36–0.94) than the both SGLT2i and diuretics group. This study indicates that diuretics could raise the risk of CKD in diabetic patients, but when used in combination with SGLT2i, they continue to offer protection against CKD.","PeriodicalId":501597,"journal":{"name":"BMC Pharmacology and Toxicology","volume":"79 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140034875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immuno-oncological effects of standard anticancer agents and commonly used concomitant drugs: an in vitro assessment","authors":"Tove Selvin, Malin Berglund, Lena Lenhammar, Magnus Lindskog, Malin Jarvius, Rolf Larsson, Peter Nygren, Mårten Fryknäs, Claes R Andersson","doi":"10.1186/s40360-024-00746-6","DOIUrl":"https://doi.org/10.1186/s40360-024-00746-6","url":null,"abstract":"It has become evident in the field of oncology that the outcome of medical treatment is influenced by the combined effect exerted on both cancer- and immune cells. Therefore, we evaluated potential immunological effects of 46 standard anticancer agents and 22 commonly administered concomitant non-cancer drugs. We utilized a miniaturized in vitro model system comprised of fluorescently labeled human colon and lung cancer cell lines grown as monocultures and co-cultured with activated peripheral blood mononuclear cells (PBMCs). The Bliss Independence Model was then applied to detect antagonism and synergy between the drugs and activated immune cells. Among the standard anticancer agents, tyrosine kinase inhibitors (TKIs) stood out as the top inducers of both antagonism and synergy. Ruxolitinib and dasatinib emerged as the most notably antagonistic substances, exhibiting the lowest Bliss scores, whereas sorafenib was shown to synergize with activated PBMCs. Most concomitant drugs did not induce neither antagonism nor synergy. However, the statins mevastatin and simvastatin were uniquely shown to synergize with activated PBMC at all tested drug concentrations in the colon cancer model. We utilized a miniaturized tumor-immune model to enable time and cost-effective evaluation of a broad panel of drugs in an immuno-oncology setting in vitro. Using this approach, immunomodulatory effects exerted by TKIs and statins were identified.","PeriodicalId":501597,"journal":{"name":"BMC Pharmacology and Toxicology","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140034878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation and evaluation of transdermal permeation of Huperzine A ethosomes gel in vitro","authors":"Jiyu Wu, Renai Xu, Xiaowei Xu, Shiyuan Ye, Aifang Huang","doi":"10.1186/s40360-024-00742-w","DOIUrl":"https://doi.org/10.1186/s40360-024-00742-w","url":null,"abstract":"This study aimed to design and evaluate the transdermal permeation of Huperzine A ethosomes gel in vitro. Huperzine A ethosomes were prepared using the injection method, and their physical and chemical properties were characterized. A comparison was made between Huperzine A ethosomes gel, ordinary gel, and cream. The Franz diffusion cell test on mouse abdominal skin was conducted, and Huperzine A concentration was determined using LC-MS/MS. Transdermal volume, skin retention, and transdermal rate were used to assess the percutaneous permeability of the three preparations. Results demonstrated that Huperzine A ethosomes gel exhibited significantly higher accumulative permeation, transdermal rate, and skin retention compared to ordinary gel and cream. The findings suggest that Huperzine A ethosomes gel, with its controllable quality and favorable transdermal absorption properties, holds potential as a safe option for clinical administration.","PeriodicalId":501597,"journal":{"name":"BMC Pharmacology and Toxicology","volume":"166 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139969007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of the median lethal dose of zinc gluconate in mice and safety evaluation","authors":"Yong-cai Wang, Xia Yang, Juan Xiao, Su-mei Wei, Ying Su, Xiu-qi Chen, Ting Huang, Qing-wen Shan","doi":"10.1186/s40360-024-00736-8","DOIUrl":"https://doi.org/10.1186/s40360-024-00736-8","url":null,"abstract":"Zinc Gluconate (ZG) is a safe and effective supplement for zinc. However, there is limited research on the optimal dosage for intravenous injection and the safety evaluation of animal models for ZG. This study aims to determine the safe dose range of ZG for intravenous injection in C57BL/6J mice. A Dose titration experiment was conducted to determine the LD50 and 95% confidence interval (95%CI) of ZG in mice. Based on the LD50, four sub-lethal doses (SLD) of ZG were evaluated. Following three injections of each SLD and monitoring for seven days, serum zinc levels were measured, and pathological changes in the liver, kidney, and spleen tissues of mice were determined by histological staining. The dose titration experiment determined the LD50 of ZG in mice to be 39.6 mg/kg, with a 95%CI of 31.8-49.3 mg/kg. There was a statistically significant difference in the overall serum zinc levels (H = 36.912, P < 0.001) following SLD administration. Pairwise comparisons showed that the serum zinc levels of the 1/2 LD50 and 3/4 LD50 groups were significantly higher than those of the control group (P < 0.001); the serum zinc level of the 3/4 LD50 group was significantly higher than those of the 1/8 LD50 and 1/4 LD50 groups (P < 0.05). There was a positive correlation between the different SLDs of ZG and the serum zinc levels in mice (rs = 0.973, P < 0.001). H&E staining showed no significant histological abnormalities or lesions in the liver, kidney, and spleen tissues of mice in all experimental groups. The appropriate dose range of ZG for intravenous injection in C57BL/6J mice was clarified, providing a reference for future experimental research.","PeriodicalId":501597,"journal":{"name":"BMC Pharmacology and Toxicology","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139688509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of uranium toxicity and uranium-induced oxidative stress in advancing kidney injury and endothelial inflammation in rats","authors":"Yuwei Yang, Chunmei Dai, Xi Chen, Bin Zhang, Xiaohan Li, Wenyu Yang, Jun Wang, Jiafu Feng","doi":"10.1186/s40360-024-00734-w","DOIUrl":"https://doi.org/10.1186/s40360-024-00734-w","url":null,"abstract":"Uranium exposure may cause serious pathological injury to the body, which is attributed to oxidative stress and inflammation. However, the pathogenesis of uranium toxicity has not been clarified. Here, we evaluated the level of oxidative stress to determine the relationship between uranium exposure, nephrotoxic oxidative stress, and endothelial inflammation. Forty male Sprague–Dawley rats were divided into three experimental groups (U-24h, U-48h, and U-72h) and one control group. The three experimental groups were intraperitoneally injected with 2.0 mg/kg uranyl acetate, and tissue and serum samples were collected after 24, 48, and 72 h, respectively, whereas the control group was intraperitoneally injected with 1.0 ml/kg normal saline and samples were collected after 24 h. Then, we observed changes in the uranium levels and oxidative stress parameters, including the total oxidative state (TOS), total antioxidant state (TAS), and oxidative stress index (OSI) in kidney tissue and serum. We also detected the markers of kidney injury, namely urea (Ure), creatine (Cre), cystatin C (CysC), and neutrophil gelatinase-associated lipocalin (NGAL). The endothelial inflammatory markers, namely C-reactive protein (CRP), lipoprotein phospholipase A2 (Lp-PLA2), and homocysteine (Hcy), were also quantified. Finally, we analyzed the relationship among these parameters. TOS (z = 3.949; P < 0.001), OSI (z = 5.576; P < 0.001), Ure (z = 3.559; P < 0.001), Cre (z = 3.476; P < 0.001), CysC (z = 4.052; P < 0.001), NGAL (z = 3.661; P < 0.001), and CRP (z = 5.286; P < 0.001) gradually increased after uranium exposure, whereas TAS (z = −3.823; P < 0.001), tissue U (z = −2.736; P = 0.001), Hcy (z = −2.794; P = 0.005), and Lp-PLA2 (z = −4.515; P < 0.001) gradually decreased. The serum U level showed a V-shape change (z = −1.655; P = 0.094). The uranium levels in the kidney tissue and serum were positively correlated with TOS (r = 0.440 and 0.424; P = 0.005 and 0.007) and OSI (r = 0.389 and 0.449; P = 0.013 and 0.004); however, serum U levels were negatively correlated with TAS (r = −0.349; P = 0.027). Partial correlation analysis revealed that NGAL was closely correlated to tissue U (rpartial = 0.455; P = 0.003), CysC was closely correlated to serum U (rpartial = 0.501; P = 0.001), and Lp-PLA2 was closely correlated to TOS (rpartial = 0.391; P = 0.014), TAS (rpartial = 0.569; P < 0.001), and OSI (rpartial = −0.494; P = 0.001). Pearson correlation analysis indicated that the Hcy levels were negatively correlated with tissue U (r = −0.344; P = 0.030) and positively correlated with TAS (r = 0.396; P = 0.011). The uranium-induced oxidative injury may be mainly reflected in enhanced endothelial inflammation, and the direct chemical toxicity of uranium plays an important role in the process of kidney injury, especially in renal tubular injury. In addition, CysC may be a sensitive marker reflecting the nephrotoxicity of uranium; however, Hcy is not suitable for evaluating short-te","PeriodicalId":501597,"journal":{"name":"BMC Pharmacology and Toxicology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139662354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug-drug interaction assessment based on a large-scale spontaneous reporting system for hepato- and renal-toxicity, and thrombocytopenia with concomitant low-dose methotrexate and analgesics use","authors":"Takeshi Honma, Kenji Onda, Koichi Masuyama","doi":"10.1186/s40360-024-00738-6","DOIUrl":"https://doi.org/10.1186/s40360-024-00738-6","url":null,"abstract":"Methotrexate (MTX) is the cornerstone of rheumatoid arthritis (RA) treatment and is highly effective with low-dose intermittent administration. MTX is occasionally used in combination with non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (APAP)/paracetamol for pain or inflammation control. With MTX treatment, the side effects, such as hepatotoxicity, renal failure, and myelosuppression should be considered. These are also seen with analgesics treatment. We used a large spontaneously reported adverse event database (FAERS [JAPIC AERS]) to analyze whether the reporting of adverse events increased upon MTX and analgesic therapy in patients with RA. After identifying RA cases, the crude reporting odds ratios (cRORs) for hepatotoxicity, renal failure, and thrombocytopenia associated with the use of MTX, APAP, or NSAIDs were calculated by disproportionality analysis, which revealed significantly higher cRORs for these events. No analgesics showed consistent positive signals for drug-drug interaction (DDI) with concomitant low-dose MTX analyzed using four algorithms for DDI interaction (the Ω shrinkage measure, additive or multiplicative, and combination risk ratio models). However, in renal failure and thrombocytopenia, loxoprofen (Ω025 = 0.08) and piroxicam (Ω025 = 0.46), and ibuprofen (Ω025 = 0.74) and ketorolac (Ω025 = 3.52), respectively, showed positive signals in the Ω shrinkage measure model, and no consistency was found among adverse events or NSAIDs. Studies using spontaneous reporting systems have limitations such as reporting bias or lack of patient background; however, the results of our comprehensive analysis support the results of previous clinical or epidemiological studies. This study also demonstrated the usefulness of FAERS for DDI assessment.","PeriodicalId":501597,"journal":{"name":"BMC Pharmacology and Toxicology","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139656405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of three different prophylactic treatments for postoperative nausea and vomiting after total joint arthroplasty under general anesthesia: a randomized clinical trial","authors":"Jinwei Xie, Yingcun Cai, Fuxing Pei","doi":"10.1186/s40360-024-00735-9","DOIUrl":"https://doi.org/10.1186/s40360-024-00735-9","url":null,"abstract":"Postoperative nausea and vomiting (PONV) after total joint arthroplasty is common and associated with delayed recovery. This study was performed to evaluate the efficacy of three different prophylactic regimens for PONV after total joint arthroplasty under general anesthesia. Patients undergoing primary total hip or knee arthroplasty were randomized to Group A (ondansetron), Group B (10 mg dexamethasone plus ondansetron and mosapride), or Group C (three doses of 10 mg dexamethasone plus ondansetron and mosapride). The primary outcome was the total incidence of PONV during postoperative 48 h. The secondary outcomes were complete response, rescue antiemetic treatment, opioid consumption, time until first defecation, postoperative appetite score, satisfaction score, length of hospital stay, blood glucose level, and complications. Patients in Group C experienced a lower incidence of total PONV (29.3%, p = 0.001) and a higher incidence of complete response (70.7%, p = 0.001) than did patients in Group A (51.9%, 48.2%, respectively). Patients in Group C also experienced a lower incidence of severe PONV (4.3%) than patients in Group A (25.9%, p<0.001) and B (20.4%, p<0.001). Moreover, less rescue antiemetic treatment (1.4 ± 0.5 mg Metoclopramide) and postoperative opioid consumption (1.8 ± 0.3 mg Oxycodone, 6.0 ± 1.0 mg Pethidine) was needed in Group C. Additionally, a shorter time until first defecation, shorter length of stay, and better postoperative appetite scores and satisfaction scores were detected in patients in Group C. A slight increase in the fasting blood glucose level was observed in Group C, and the complications were comparable among the groups. Combined use of ondansetron, mosapride and three doses of dexamethasone can provide better antiemetic effectiveness, postoperative appetite, bowel function recovery, and pain relief than a single dose or ondansetron only. The protocol was registered at the Chinese Clinical Trial Registry (ChiCTR1800015896, April 27, 2018).","PeriodicalId":501597,"journal":{"name":"BMC Pharmacology and Toxicology","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139587509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Informal sale of antibiotics in Guatemalan convenience stores before and after implementation of federal antibiotic dispensing legislation","authors":"N. Rojop, P. Moreno, L. Grajeda, J. Romero, L. Reynoso, E. Muñoz, G. H. Palmer, C. Cordón-Rosales, D. R. Call, B. M. Ramay","doi":"10.1186/s40360-023-00720-8","DOIUrl":"https://doi.org/10.1186/s40360-023-00720-8","url":null,"abstract":"Convenience stores in Guatemala provide essential consumer goods in communities, but many dispense antibiotics illegally. Federal legislation, passed in August of 2019, requires prescriptions for antibiotic purchase at pharmacies but it is unclear if this legislation is enforced or if it has any impact on unlawful sales of antibiotics. To determine if antibiotic availability changed in convenience stores, we carried out a repeated measures study collecting antibiotic availability data before and after implementation of the dispensing regulation. There was no statistical difference in the proportion of convenience stores that sold antibiotics before and after antibiotic regulations [66.6% (295/443) and 66.7% (323/484), respectively, P>0.96], nor in the number of stores selling amoxicillin [55.5% (246/443) and 52.3% (253/484), respectively, P>0.96], but fewer stores (20%) sold tetracycline capsules after regulation was passed (P<0.05). For stores visited both before and after passage of legislation (n=157), 15% stopped selling antibiotics while 25% started selling antibiotics. Antibiotics from convenience stores were reportedly sold for use in people and animals. Antibiotics remain widely available in convenience stores consistent with no significant change in the informal sector after implementation of prescription requirements for pharmacies. Importantly, effects from regulatory change could have been masked by potential changes in antibiotic use during the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic.","PeriodicalId":501597,"journal":{"name":"BMC Pharmacology and Toxicology","volume":"7 3-4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139562247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enoxaparin for VTE thromboprophylaxis during inpatient rehabilitation care: assessment of the standard fixed dosing regimen","authors":"Amir Haim, Orli Avnery, Deborah Rubin-Asher, Hagay Amir, Kaifa Hashem, Harel Ben Zvi, Motti Ratmansky","doi":"10.1186/s40360-023-00728-0","DOIUrl":"https://doi.org/10.1186/s40360-023-00728-0","url":null,"abstract":"We aimed to examine the efficiency of fixed daily dose enoxaparin (40 mg) thromboprophylaxis strategy for patients undergoing inpatient rehabilitation. This was an observational, prospective, cohort study that included 63 hospitalized patients undergoing rehabilitative treatment following sub-acute ischemic stroke (SAIS) or spinal cord injury (SCI), with an indication for thromboprophylaxis. Anti-Xa level measured three hours post-drug administration (following three consecutive days of enoxaparin treatment or more) was utilised to assess in vivo enoxaparin activity. An anti-Xa level between 0.2-0.5 U/ml was considered evidence of effective antithrombotic activity. We found sub-prophylactic levels of anti-Xa (<0.2 U/ml) in 19% (12/63). Results were within the recommended prophylactic range (0.2-0.5 U/ml) in 73% (46/63) and were supra-prophylactic (>0.5 U/ml) in 7.9% (5/63) of patients. Anti-Xa levels were found to inversely correlate with patients’ weight and renal function as defined by creatinine clearance (CrCl) (p<0.05). Our study confirmed that a one-size-fits-all approach for venous thromboembolism (VTE) prophylaxis may be inadequate for rehabilitation patient populations. The efficacy of fixed-dose enoxaparin prophylaxis is limited and may be influenced by renal function and weight. This study suggests that anti-Xa studies and prophylactic enoxaparin dose adjustments should be considered in certain patients, such as those who are underweight, overweight and or have suboptimal renal function. No. NCT103593291, registered August 2018. • Clinicians should be aware that fixed dose enoxaparin prophylaxis will only provide adequate therapeutic response for a proportion of rehabilitation patients. • The efficacy of fixed-dose enoxaparin prophylaxis is limited and may be influenced by renal function and weight. • A personalized approach to VTE prophylaxis that includes anit-Xa studies and prophylactic dose adjustments should be considered in certain patients, such as those who are underweight, overweight and or have suboptimal renal function. • More studies are required to investigate the interaction of weight and creatinine in order to establish VTE prophylactic dosing guidelines for specific rehabilitation populations.","PeriodicalId":501597,"journal":{"name":"BMC Pharmacology and Toxicology","volume":"64 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139408314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-biased gene expression and gene-regulatory networks of sex-biased adverse event drug targets and drug metabolism genes","authors":"Jennifer L. Fisher, Amanda D. Clark, Emma F. Jones, Brittany N. Lasseigne","doi":"10.1186/s40360-023-00727-1","DOIUrl":"https://doi.org/10.1186/s40360-023-00727-1","url":null,"abstract":"Previous pharmacovigilance studies and a retroactive review of cancer clinical trial studies identified that women were more likely to experience drug adverse events (i.e., any unintended effects of medication), and men were more likely to experience adverse events that resulted in hospitalization or death. These sex-biased adverse events (SBAEs) are due to many factors not entirely understood, including differences in body mass, hormones, pharmacokinetics, and liver drug metabolism enzymes and transporters. We first identified drugs associated with SBAEs from the FDA Adverse Event Reporting System (FAERS) database. Next, we evaluated sex-specific gene expression of the known drug targets and metabolism enzymes for those SBAE-associated drugs. We also constructed sex-specific tissue gene-regulatory networks to determine if these known drug targets and metabolism enzymes from the SBAE-associated drugs had sex-specific gene-regulatory network properties and predicted regulatory relationships. We identified liver-specific gene-regulatory differences for drug metabolism genes between males and females, which could explain observed sex differences in pharmacokinetics and pharmacodynamics. In addition, we found that ~ 85% of SBAE-associated drug targets had sex-biased gene expression or were core genes of sex- and tissue-specific network communities, significantly higher than randomly selected drug targets. Lastly, we provide the sex-biased drug-adverse event pairs, drug targets, and drug metabolism enzymes as a resource for the research community. Overall, we provide evidence that many SBAEs are associated with drug targets and drug metabolism genes that are differentially expressed and regulated between males and females. These SBAE-associated drug metabolism enzymes and drug targets may be useful for future studies seeking to explain or predict SBAEs.","PeriodicalId":501597,"journal":{"name":"BMC Pharmacology and Toxicology","volume":"103 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139079713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}