Basic & Clinical Pharmacology & Toxicology最新文献

{"title":"Initiation of Anticoagulants During the COVID-19 Pandemic in Sweden: An Interrupted Time Series Analysis","authors":"Per-Jostein Samuelsen,&nbsp;Björn Wettermark,&nbsp;Fredrik Nyberg,&nbsp;Mohammadhossein Hajiebrahimi","doi":"10.1111/bcpt.14119","DOIUrl":"10.1111/bcpt.14119","url":null,"abstract":"<p>The COVID-19 pandemic may have increased anticoagulant initiation due to the thrombogenic nature of the disease or decreased due to the societal impact of the pandemic. We aimed to study the effect of the COVID-19 pandemic on initiation of anticoagulants in Sweden. We conducted a single interrupted time series analysis on the monthly cumulative incidence of nonvitamin K antagonist oral anticoagulants (NOAC), warfarin, or heparins, before and after March 2020, using SCIFI-PEARL dataset. For anticoagulants in total, there were no statistically significant changes or differences in the trends of initiation after the start of the pandemic. There was a slight numerical decrease in initiation after the onset of the pandemic, particularly for NOACs. For individuals aged ≥ 65 years, however, the immediate decrease in initiation was considerable for NOACs. The prepandemic declining trend of warfarin initiation seemed to attenuate, that is, became less negative, after March 2020. We did not find any profound effect of the COVID-19 pandemic on the initiation of anticoagulants in total. However, among individuals aged ≥ 65 years, a notable immediate decrease in initiation of NOACs was observed. Furthermore, the onset of the pandemic may have attenuated the downward temporal trend in initiation of warfarin use.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.14119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"List of Reviewers for the January 2025 Issue","authors":"","doi":"10.1111/bcpt.14122","DOIUrl":"https://doi.org/10.1111/bcpt.14122","url":null,"abstract":"","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143110738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BCPT 2024 Prizes and Awards","authors":"Jens Lykkesfeldt,&nbsp;Ulf Simonsen","doi":"10.1111/bcpt.14123","DOIUrl":"10.1111/bcpt.14123","url":null,"abstract":"","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Effects of Baicalein and Bergenin Against Gentamicin-Induced Hepatic and Renal Injuries in Rats: An Immunohistochemical and Biochemical Study","authors":"Fazile Nur Ekinci Akdemir,&nbsp;Serkan Yildirim,&nbsp;Fatih Mehmet Kandemir,&nbsp;Sefa Küçükler,&nbsp;Ersen Eraslan,&nbsp;Mustafa Can Güler","doi":"10.1111/bcpt.14121","DOIUrl":"10.1111/bcpt.14121","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Drug-induced organ toxicity is a significant health concern, with gentamicin known for its effective antibacterial properties but also severe side effects, particularly cytotoxicity in liver and kidney tissues. This current study observed the preventive role of baicalein and bergenin against hepatic and renal injuries caused by gentamicin in rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirty-two male Sprague Dawley rats were divided into four groups, namely, control, gentamicin (gentamicin 80 mg/kg/day), baicalein (gentamicin 80 mg/kg/day + baicalein 100 mg/kg/day) and bergenin (gentamicin 80 mg/kg/day + bergenin 100 mg/kg/day). Hepatotoxicity and nephrotoxicity were induced by giving gentamicin (80 mg/kg/day). We evaluated the biochemical markers, including alkaline phosphatase (ALP), urea, alanine transaminase (ALT), creatinine and aspartate transaminase (AST) levels, antioxidant enzymes, oxidative stress parameters and histopathological and immunohistochemical changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Gentamicin increased oxidative stress parameters and decreased antioxidant activity. The treatment with baicalein and bergenin significantly restored these markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Baicalein and bergenin significantly mitigated gentamicin-induced hepatic and renal toxicity by restoring biochemical markers, reducing oxidative stress and enhancing antioxidant enzyme activity. Histopathological and immunohistochemical analyses confirmed the protective effects of both compounds against organ damage. No statistically significant differences were observed between the two drugs for these parameters. These results suggest their potential as therapeutic agents to prevent gentamicin-induced organ toxicity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical Evidence for a Drug–Drug Interaction Between Cannabinol and Melatonin","authors":"Lyndsey L. Anderson,&nbsp;Nicole A. Hawkins,&nbsp;Ka Lai Yip,&nbsp;Michael Udoh,&nbsp;Jennifer A. Kearney,&nbsp;Jonathon C. Arnold","doi":"10.1111/bcpt.14120","DOIUrl":"10.1111/bcpt.14120","url":null,"abstract":"<div>\u0000 \u0000 <p>The worldwide legalization of medicinal cannabis has led to an increased use of products made by commercial operators. These products often contain minor cannabinoids such as cannabinol (CBN) which are advertised to improve sleep. Products are also available in which CBN is combined with conventional therapies, with a common product containing both CBN and the widely used sleep-aid melatonin. The combination of CBN and melatonin provides potential for a pharmacokinetic drug–drug interaction (DDI) given that cannabinoids are known to inhibit drug-metabolizing enzymes. Indeed, we recently reported that CBN potently inhibited the CYP1A2-mediated metabolism of caffeine. CYP1A2 is the major hepatic enzyme involved in the metabolism of melatonin; thus, in this study, we aimed to examine whether CBN inhibited CYP1A2-mediated metabolism of melatonin in vitro and in vivo. We found CBN potently inhibited CYP1A2-mediated metabolism of melatonin and increased the apparent oral bioavailability of melatonin in mice with a four-fold increase in the plasma melatonin exposure. Our results provide an additional example of a potential DDI involving melatonin.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Ethanol Concentrations in Relation to Sex and Age in Patients Admitted to a Large Emergency Department During 2015–2020","authors":"Aase Bratberg,&nbsp;Ilah Nygaard,&nbsp;Kari Løhne,&nbsp;Ingebjørg Gustavsen,&nbsp;Mimi Stokke Opdal","doi":"10.1111/bcpt.14118","DOIUrl":"10.1111/bcpt.14118","url":null,"abstract":"<p>We examined the number of patients tested for serum ethanol concentration (SEC) at admission to a large Emergency Department (ED) and the relationship of SEC with sex and age. SEC was analysed by enzymatic method. We retrieved SEC in patient samples from the ED during 2015–2020 from the laboratory information system. Altogether, 174 378 patients were admitted, and 7.3% were tested for SEC. Of these, 35.3% had a positive test. The percentage of patients tested increased from 4.8% in 2015 to 14.4% in 2020. A total of 416 patients had more than one positive SEC. For individual data, we included the first positive test per patient, <i>n</i> = 3607. Of these, 73% were men and 27% were women. The median SEC for both men and women was 1.9 g/L. About 4.4% had a SEC ≥ 3.5 g/L. The median SEC in patients aged 30–59 years was 0.2 g/L higher than the 12–29 and ≥ 60 age groups. In conclusion, the increase in the percentage of patients tested did not lead to a corresponding increase in ethanol-positive tests. There was a large predominance of men, the median SEC was the same for men and women and highest in the 30–59 age group.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic and Additive Inhibition of UDP-Glucuronosyltransferase 1A9 by Endogenous and Foodborne Inhibitors","authors":"Ruixue Li,&nbsp;Ling Xiao,&nbsp;Wenjuan Li,&nbsp;Wenjing Li,&nbsp;Kuan Zhao,&nbsp;Liangliang Zhu","doi":"10.1111/bcpt.14116","DOIUrl":"10.1111/bcpt.14116","url":null,"abstract":"<div>\u0000 \u0000 <p>UDP-glucuronosyltransferases (UGTs) are responsible for inactivation of a variety of drugs, endogenous hormones and environmental toxicants. Chemical inhibitors are a common factor decreasing UGT activities and furtherly inducing health problems. Although simultaneously encountering different inhibitors is readily to occur, no information is available for combined inhibition of UGT. This in vitro study investigates the combined inhibition of human UGT1A9 by endogenous and foodborne inhibitors (magnolol, di-bromophenols, UDP). <i>J</i> values (the ratio of inhibitory rate to the remaining activity) are analysed to determine the combined inhibition type. The combined inhibition of di-bromophenols and UDP obeys additive inhibition, in which combined <i>J</i> values equal to the sum of individual <i>J</i> values in alone inhibition assays. Meanwhile, there is a synergistic effect between 2,4-di-bromophenol and magnolol with combination index values ranging from 0.10 to 0.85. Further assays indicate that 2,4-di-bromophenol decreases IC₅₀ values for magnolol and vice versa. Kinetic analysis confirms that the two inhibitors and UGT1A9 can form a ternary complex with the inhibition constants of 0.0188 μM (magnolol) and 0.634 (2,4-di-bromophenol) μM. In summary, this study demonstrates that besides additive inhibition, synergistic inhibition is a probable occurrence in combined inhibition of UGT. It is suggested that the inhibitors can increase mutual inhibitory effects which deserves attentions in future UGT inhibition related studies.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased blood pressure with acute administration of quercetin in L-NAME-induced hypertensive rats","authors":"Siluleko A. Mkhize,&nbsp;Refentshe A. Nthlane,&nbsp;Sanelisiwe P. Xhakaza,&nbsp;Peter D. Verhaert,&nbsp;Sooraj Baijnath,&nbsp;Aletta M. E. Millen,&nbsp;Frederic S. Michel","doi":"10.1111/bcpt.14113","DOIUrl":"10.1111/bcpt.14113","url":null,"abstract":"<p>Quercetin is known to reduce blood pressure (BP); however, its acute effects are unclear. We investigated the acute effects of quercetin on BP, aortic mechanical properties and vascular reactivity in female Sprague–Dawley (SD) rats. Hypertension was induced using L-NAME (40 mg/kg/day). Quercetin (4.5 mg/kg) was administered intravenously. Mechanical properties of the aortae were measured by echo-tracking in normotensive and hypertensive rats. L-NAME and quercetin quantities in the aorta were determined using AP-MALDI-MSI. Vascular reactivity was performed in mesenteric and renal arteries. L-NAME increased BP and PWVβ while decreasing strain. Quercetin decreased BP and ameliorated PWVβ in L-NAME-induced hypertensive rats. Ex vivo, the acetylcholine (ACh)-induced increase in tension at 100 μM was reduced in renal arteries when exposed to quercetin while phenylephrine (Phe)-induced contractile response was augmented. In quiescent rings of renal arteries incubated with L-NAME (10 μM) and TRAM-34 (1 μM), the ACh-induced vasoconstrictions were inhibited by quercetin. Quercetin resulted in concentration-dependent vasodilation in mesenteric arteries and increased its sensitivity to ACh-induced relaxations. Quercetin lowered BP in L-NAME-induced hypertensive rats, likely due to changes in aortic mechanical properties and relaxation of resistance arteries. Further research is warranted to clarify the acute effects of quercetin on renal arteries in this hypertensive model.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.14113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efflux and uptake transport and gut microbial reactivation of raloxifene glucuronides","authors":"Arttu Uoti,&nbsp;Mika Kurkela,&nbsp;Mikko Niemi,&nbsp;Timo Oksanen,&nbsp;Stefan Oswald,&nbsp;Lauri Puustinen,&nbsp;Heidi Kidron,&nbsp;Noora Sjöstedt","doi":"10.1111/bcpt.14107","DOIUrl":"10.1111/bcpt.14107","url":null,"abstract":"<p>Raloxifene has low bioavailability due to extensive glucuronidation in the intestine and the liver, and its pharmacokinetics is associated with high intra- and interindividual variability. Some of this variability could be explained by the enterohepatic recycling of raloxifene, which is driven by transporter-mediated uptake and efflux and gut microbial deglucuronidation of raloxifene glucuronides. These individual processes involved in raloxifene disposition, however, have not been characterized in full detail. In this study, we evaluated the interactions of raloxifene and its three glucuronide metabolites (raloxifene 4′-glucuronide, raloxifene 6-glucuronide and raloxifene 4′,6-diglucuronide) with drug transporters using Sf9 membrane vesicles and HEK293 cells. Additionally, we measured the deglucuronidation of raloxifene glucuronides in human faecal extracts. All raloxifene glucuronides were transported by MRP2 and MRP3, whereas raloxifene monoglucuronides were identified as substrates of OATP1B1, OATP1B3 and OATP2B1. All three raloxifene glucuronides were readily deglucuronidated in the presence of faecal extracts, although with high between-subject variability. The results of this study provide further understanding of the disposition of raloxifene, which can help understand the sources behind the interindividual variability in raloxifene pharmacokinetics.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.14107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What participants are told about receiving trial results when they consent to participate in a trial","authors":"Rafael Dal-Ré,&nbsp;Arthur L. Caplan,&nbsp;Søren Holm,&nbsp;Reecha Sofat,&nbsp;Richard Stephens","doi":"10.1111/bcpt.14115","DOIUrl":"10.1111/bcpt.14115","url":null,"abstract":"<p>In a 2022 consultation, the UK public highlighted the need to disseminate trial results to participants. We assess whether the information provided to trial participants in publicly available participant information sheets (PISs) of trials conducted in the UK is helpful for future trials. This cross-sectional study is based on a search conducted on 18 August 2023 on ClinicalTrials.gov looking for UK completed or terminated phase 2–4 medicine trials. The posted PIS (or the protocol, if the PIS was unavailable) were reviewed checking the text used to inform participants on how results will be disseminated to participants. Of the 48 records retrieved, 32 were included: 23 and 9 had the PIS or the protocol posted, respectively. Seven (22%) did not mention dissemination of results to participants. Thirteen (41%) used the same short “common, standard text” of four sentences to inform participants. This text mentioned ClinicalTrials.gov as the source for further information and US Law as the reason for it. Twelve (38%) used different texts with different scopes and lengths. These results showed that publicly available PISs of medicinal product trials conducted in the UK are very limited and of scarce utility for investigators aiming to start a new trial.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}