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Initiation of Anticoagulants During the COVID-19 Pandemic in Sweden: An Interrupted Time Series Analysis 瑞典COVID-19大流行期间抗凝血剂的启动:中断时间序列分析。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-05 DOI: 10.1111/bcpt.14119
Per-Jostein Samuelsen, Björn Wettermark, Fredrik Nyberg, Mohammadhossein Hajiebrahimi

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.

COVID-19大流行可能由于该疾病的致血栓性而增加了抗凝剂的使用,也可能由于大流行的社会影响而减少了抗凝剂的使用。我们的目的是研究COVID-19大流行对瑞典开始使用抗凝血剂的影响。我们使用SCIFI-PEARL数据集对2020年3月前后非维生素K拮抗剂口服抗凝剂(NOAC)、华法林或肝素的月累积发病率进行了单中断时间序列分析。总的来说,在大流行开始后,抗凝剂的使用趋势没有统计学上的显著变化或差异。在大流行开始后,特别是对国家和地区国家而言,启动数量略有减少。然而,对于年龄≥65岁的个体,NOACs的起始率立即下降相当大。在2020年3月之后,华法林大流行前的下降趋势似乎减弱,即变得不那么消极。总的来说,我们没有发现COVID-19大流行对抗凝剂的使用有任何深刻的影响。然而,在年龄≥65岁的个体中,观察到NOACs的起始率显着立即下降。此外,大流行的爆发可能减弱了华法林开始使用的时间下降趋势。
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引用次数: 0
List of Reviewers for the January 2025 Issue
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-02 DOI: 10.1111/bcpt.14122
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引用次数: 0
BCPT 2024 Prizes and Awards BCPT 2024获奖情况。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-26 DOI: 10.1111/bcpt.14123
Jens Lykkesfeldt, Ulf Simonsen
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引用次数: 0
Protective Effects of Baicalein and Bergenin Against Gentamicin-Induced Hepatic and Renal Injuries in Rats: An Immunohistochemical and Biochemical Study 黄芩素和卑尔根素对庆大霉素致大鼠肝肾损伤的保护作用:免疫组织化学和生化研究。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-26 DOI: 10.1111/bcpt.14121
Fazile Nur Ekinci Akdemir, Serkan Yildirim, Fatih Mehmet Kandemir, Sefa Küçükler, Ersen Eraslan, Mustafa Can Güler

Background

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.

Methods

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.

Results

Gentamicin increased oxidative stress parameters and decreased antioxidant activity. The treatment with baicalein and bergenin significantly restored these markers.

Conclusions

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.

背景:药物诱导的器官毒性是一个重要的健康问题,庆大霉素以其有效的抗菌特性而闻名,但也有严重的副作用,特别是对肝脏和肾脏组织的细胞毒性。本研究观察了黄芩素和卑尔根素对庆大霉素致大鼠肝、肾损伤的预防作用。方法:雄性sd大鼠32只,随机分为4组,分别为对照组、庆大霉素组(庆大霉素80 mg/kg/d)、黄芩素组(庆大霉素80 mg/kg/d +黄芩素100 mg/kg/d)和豆根素组(庆大霉素80 mg/kg/d +豆根素100 mg/kg/d)。庆大霉素(80 mg/kg/d)引起肝毒性和肾毒性。我们评估了生化指标,包括碱性磷酸酶(ALP)、尿素、丙氨酸转氨酶(ALT)、肌酐和天冬氨酸转氨酶(AST)水平、抗氧化酶、氧化应激参数以及组织病理学和免疫组织化学变化。结果:庆大霉素增加氧化应激参数,降低抗氧化活性。黄芩素和卑尔根素处理显著恢复了这些标记。结论:黄芩素和卑尔根素可通过恢复生化指标、降低氧化应激和增强抗氧化酶活性,显著减轻庆大霉素引起的肝、肾毒性。组织病理学和免疫组织化学分析证实了这两种化合物对器官损伤的保护作用。两种药物在这些参数上没有统计学上的显著差异。这些结果表明它们有可能作为治疗药物来预防庆大霉素引起的器官毒性。
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引用次数: 0
Preclinical Evidence for a Drug–Drug Interaction Between Cannabinol and Melatonin 大麻酚和褪黑素之间药物相互作用的临床前证据。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-25 DOI: 10.1111/bcpt.14120
Lyndsey L. Anderson, Nicole A. Hawkins, Ka Lai Yip, Michael Udoh, Jennifer A. Kearney, Jonathon C. Arnold

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.

药用大麻在世界范围内的合法化导致越来越多地使用商业经营者生产的产品。这些产品通常含有少量的大麻素,如大麻酚(CBN),它被宣传为可以改善睡眠。还有一些产品将CBN与传统疗法结合使用,一种常见的产品同时含有CBN和广泛使用的助眠褪黑激素。鉴于大麻素已知可抑制药物代谢酶,CBN和褪黑素的组合为药代动力学药物-药物相互作用(DDI)提供了潜力。事实上,我们最近报道了CBN有效抑制cyp1a2介导的咖啡因代谢。CYP1A2是参与褪黑素代谢的主要肝脏酶;因此,在本研究中,我们旨在研究CBN是否在体外和体内抑制cyp1a2介导的褪黑激素代谢。我们发现CBN能有效地抑制cyp1a2介导的褪黑素代谢,并增加褪黑素的口服生物利用度,使血浆褪黑素暴露增加四倍。我们的结果提供了一个涉及褪黑素的潜在DDI的额外例子。
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引用次数: 0
Serum Ethanol Concentrations in Relation to Sex and Age in Patients Admitted to a Large Emergency Department During 2015–2020 2015-2020年大型急诊科住院患者血清乙醇浓度与性别和年龄的关系
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-25 DOI: 10.1111/bcpt.14118
Aase Bratberg, Ilah Nygaard, Kari Løhne, Ingebjørg Gustavsen, Mimi Stokke Opdal

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, n = 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.

我们研究了在一家大型急诊科(ED)入院时检测血清乙醇浓度(SEC)的患者数量,以及SEC与性别和年龄的关系。用酶法对SEC进行分析。我们从实验室信息系统中检索2015-2020年间急诊科患者样本中的SEC。总共有174 378名患者入院,7.3%的患者接受了SEC检测,其中35.3%的患者检测呈阳性。接受检测的患者比例从2015年的4.8%增加到2020年的14.4%。共有416例患者有一个以上的SEC阳性。对于个体数据,我们纳入了每个患者的第一个阳性检测,n = 3607。其中73%是男性,27%是女性。男性和女性的中位数SEC均为1.9 g/L。约4.4%的人SEC≥3.5 g/L。30-59岁患者的中位SEC比12-29岁和≥60岁年龄组高0.2 g/L。总之,接受检测的患者百分比的增加并没有导致乙醇阳性检测的相应增加。男性占多数,男性和女性的中位数SEC相同,在30-59岁年龄组中最高。
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引用次数: 0
Synergistic and Additive Inhibition of UDP-Glucuronosyltransferase 1A9 by Endogenous and Foodborne Inhibitors 内源性和食源性抑制剂对udp -葡萄糖醛酸糖基转移酶1A9的协同和加性抑制作用。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-25 DOI: 10.1111/bcpt.14116
Ruixue Li, Ling Xiao, Wenjuan Li, Wenjing Li, Kuan Zhao, Liangliang Zhu

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). J 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 J values equal to the sum of individual J 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.

udp -葡萄糖醛酸转移酶(UGTs)负责多种药物,内源性激素和环境毒物的失活。化学抑制剂是降低UGT活性并进一步诱发健康问题的常见因素。虽然同时遇到不同的抑制剂很容易发生,但没有关于联合抑制UGT的信息。这项体外研究考察了内源性和食源性抑制剂(厚朴酚、二溴酚、UDP)对人UGT1A9的联合抑制作用。通过分析J值(抑制率与剩余活性的比值)来确定联合抑制类型。二溴酚和UDP的联合抑制服从加性抑制,其中联合J值等于单独抑制试验中单个J值的总和。同时,2,4-二溴酚与厚朴酚之间存在协同效应,组合指数在0.10 ~ 0.85之间。进一步的分析表明2,4-二溴苯酚降低厚朴酚的IC50值,反之亦然。动力学分析证实,两种抑制剂与UGT1A9可形成三元配合物,抑制常数分别为0.0188 μM(厚朴酚)和0.634 μM(2,4-二溴苯酚)。综上所述,本研究表明在UGT联合抑制中,除了加性抑制外,协同抑制也可能发生。提示抑制剂可以增强相互抑制作用,值得今后UGT抑制相关研究的关注。
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引用次数: 0
Decreased blood pressure with acute administration of quercetin in L-NAME-induced hypertensive rats 急性服用槲皮素可降低 L-NAME 诱导的高血压大鼠的血压。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-19 DOI: 10.1111/bcpt.14113
Siluleko A. Mkhize, Refentshe A. Nthlane, Sanelisiwe P. Xhakaza, Peter D. Verhaert, Sooraj Baijnath, Aletta M. E. Millen, Frederic S. Michel

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.

众所周知,槲皮素可以降低血压;然而,其急性效果尚不清楚。我们研究了槲皮素对雌性SD大鼠血压、主动脉力学性能和血管反应性的急性影响。用L-NAME (40 mg/kg/天)诱导高血压。槲皮素(4.5 mg/kg)静脉滴注。用回声追踪法测定了正常和高血压大鼠主动脉的力学性能。应用AP-MALDI-MSI测定主动脉L-NAME和槲皮素含量。在肠系膜和肾动脉进行血管反应性检查。L-NAME增加BP和PWVβ,降低菌株。槲皮素降低l - name诱导的高血压大鼠血压,改善PWVβ。体外实验结果表明,槲皮素可降低乙酰胆碱(ACh)诱导的100 μM肾动脉张力升高,而苯肾上腺素(Phe)诱导的收缩反应增强。在L-NAME (10 μM)和TRAM-34 (1 μM)培养的肾动脉静息环中,槲皮素可抑制乙酰胆碱诱导的血管收缩。槲皮素导致肠系膜动脉浓度依赖性血管舒张,并增加其对乙酰胆碱所致舒张的敏感性。槲皮素降低l - name诱导的高血压大鼠的血压,可能是由于主动脉力学特性的改变和阻力动脉的松弛。槲皮素对高血压模型肾动脉的急性作用有待进一步研究。
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引用次数: 0
Efflux and uptake transport and gut microbial reactivation of raloxifene glucuronides 雷洛昔芬葡萄糖醛酸酯的外排、摄取、转运和肠道微生物活化。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-19 DOI: 10.1111/bcpt.14107
Arttu Uoti, Mika Kurkela, Mikko Niemi, Timo Oksanen, Stefan Oswald, Lauri Puustinen, Heidi Kidron, Noora Sjöstedt

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.

雷洛昔芬由于在肠道和肝脏中广泛的葡萄糖醛酸化而具有低生物利用度,其药代动力学与个体内和个体间的高度变异性有关。雷洛昔芬的肠肝再循环是由转运体介导的摄取和外排以及雷洛昔芬葡萄糖醛酸盐的肠道微生物去糖醛酸化所驱动的。然而,这些与雷洛昔芬处置有关的个体过程尚未被详细描述。在本研究中,我们利用Sf9膜囊泡和HEK293细胞评估了雷洛昔芬及其三种葡萄糖醛酸代谢产物(雷洛昔芬4′-葡萄糖醛酸、雷洛昔芬6-葡萄糖醛酸和雷洛昔芬4′,6-二脲酸)与药物转运体的相互作用。此外,我们还测量了人类粪便提取物中雷洛昔芬葡糖苷酸的去糖醛酸化。所有雷洛昔芬葡萄糖醛酸盐均由MRP2和MRP3转运,而单雷洛昔芬葡萄糖醛酸盐被鉴定为OATP1B1、OATP1B3和OATP2B1的底物。所有三种雷洛昔芬葡糖苷在粪便提取物的存在下都很容易去葡糖苷化,尽管受试者之间存在很大的差异。本研究的结果提供了对雷洛昔芬处置的进一步了解,这有助于了解雷洛昔芬药代动力学个体间差异背后的来源。
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引用次数: 0
What participants are told about receiving trial results when they consent to participate in a trial 当参与者同意参加试验时,他们被告知收到试验结果。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-19 DOI: 10.1111/bcpt.14115
Rafael Dal-Ré, Arthur L. Caplan, Søren Holm, Reecha Sofat, Richard Stephens

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.

在2022年的咨询中,英国公众强调了向参与者传播试验结果的必要性。我们评估在英国进行的试验的公开参与者信息表(尿)中提供给试验参与者的信息是否对未来的试验有帮助。本横断面研究基于2023年8月18日在ClinicalTrials.gov上进行的搜索,该搜索旨在寻找英国完成或终止的2-4期药物试验。对发布的PIS(或协议,如果PIS不可用)进行审查,检查用于通知参与者如何将结果传播给参与者的文本。在检索到的48条记录中,包括32条:分别有23条和9条发布了PIS或协议。7个(22%)没有提到向参与者传播结果。其中13个(41%)使用了同样简短的四句话的“普通标准文本”来告知参与者。本文提到ClinicalTrials.gov作为进一步信息的来源和美国法律作为其原因。12个(38%)使用不同范围和长度的不同文本。这些结果表明,在英国进行的药品试验的公开可用的尿是非常有限的,并且对于旨在开始新试验的研究人员来说很少有用。
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引用次数: 0
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