British journal of clinical pharmacology最新文献

{"title":"Abstracts of the International Workshop on Clinical Pharmacology of HIV, Hepatitis, and other Antiviral Drugs","authors":"","doi":"10.1111/bcp.16208","DOIUrl":"https://doi.org/10.1111/bcp.16208","url":null,"abstract":"<p>Acosta, Edward, 22</p><p>Aladwani, Mary, 18</p><p>Ali, Ahlam, 22</p><p>Alpert, Pamela, 10</p><p>Anaam, Emad, 14</p><p>Anderson, Peter, 7, 10, 15, 23</p><p>Antinori, Spinello, 19</p><p>Antonucci, Miriam, 11</p><p>Arora, Priyanka, 19</p><p>Arraki Zava, Selim, 10</p><p>Arshad, Usman, 3, 18</p><p>Atoyebi, Shakir, 5</p><p>Avedissian, Sean, 20</p><p>Bamford, Alasdair, 4</p><p>Baril, Jean-Guy, 9</p><p>Barker, Nicholas, 7, 10</p><p>Barlow, Eleanor, 3</p><p>Bekker, Adrie, 21</p><p>Best, Brookie, 25</p><p>Bevers, Lisanne, 4</p><p>Bin, Jiang, 24</p><p>Bin, Su, 17–18, 20–21</p><p>Boglione-Kerrien, Christelle, 6</p><p>Bolton, Carolyn, 25</p><p>Bonora, Stefano, 11</p><p>Boucoiran, Isabelle, 9</p><p>Branchford, Brian, 7</p><p>Bérard, Anne-Marie, 9</p><p>Brooks, Kristina, 7, 10, 21–23</p><p>Brown, Ashley, 20</p><p>Brummel, Sean, 21</p><p>Buchanan, Ann, 21</p><p>Burger, David, 4, 12</p><p>Bush, Mark, 22, 25</p><p>Bushman, Lane, 7, 10, 23</p><p>Bwakura-Dangarembizi, Mutsa, 12</p><p>Calcagno, Andrea, 11</p><p>Capparelli, Edmund, 25</p><p>Carnes, Tony, 10</p><p>Carroll, Miles, 22</p><p>Castagna, Antonella, 19</p><p>Castillo-Mancilla, Jose, 10</p><p>Cattaneo, Dario, 19</p><p>Chabala, Chishala, 4, 12</p><p>Challenger, Elizabeth, 8, 13</p><p>Chandasana, Hardik, 21–22</p><p>Chen, Buyun, 15</p><p>Cheung, Amy, 25</p><p>Chiong, Justin, 8</p><p>Ciuffa, Marika, 21</p><p>Colbers, Angela, 4, 12, 21</p><p>Collins, Jon, 25</p><p>Coppinger, Corwin, 10, 23</p><p>Cottrell, Mackenzie, 16</p><p>Cox, Helen, 3, 18</p><p>Coyle, Ryan, 7, 10</p><p>Cressey, Tim, 21–22</p><p>Cruz, Kimberly, 15</p><p>Curley, Paul, 3, 14, 18</p><p>Cusato, Jessica, 11</p><p>D'Amico, Ronald, 14</p><p>Davis, Casey, 19</p><p>D'avolio, Antonio, 11</p><p>de Vries, Christiaan, 15</p><p>Denti, Paolo, 5–6</p><p>Deprez, Isabelle, 25</p><p>Dhamani, Karim, 8</p><p>Di Perri, Giovanni, 11</p><p>Dickinson, Laura, 8, 13</p><p>Dooley, Kelly, 6</p><p>Dorse, Gillian, 6</p><p>Dumas, Marie-Eve, 9</p><p>Dumond, Julie, 16</p><p>Dwyer, Andrew, 3</p><p>Ellis, Samuel, 10</p><p>Ellison, Lucas, 7, 10</p><p>Else, Laura, 8, 13</p><p>Enever, Yvanne, 8</p><p>Ferrara, Micol, 11</p><p>FitzGerald, Richard, 8, 13</p><p>Fletcher, Tom, 8, 13</p><p>Flynn, Patricia, 22</p><p>Ford, Susan, 14, 25</p><p>Fortin, Claude, 9</p><p>Franck, Bénédicte, 6</p><p>Franco, Evelyn, 20</p><p>Fréchette-Le Bel, Myriam, 9</p><p>Fromage, Yeleen, 10</p><p>Gallardo Toledo, Eduardo, 14</p><p>Gallardo-Toledo, Eduardo, 3</p><p>Gandhi, Monica, 15</p><p>Garst, Erin, 7</p><p>Gaur, Aditya, 25</p><p>Gervasoni, Cristina, 19</p><p>Ghosn, Jade, 12</p><p>Giacomelli, Andrea, 19</p><p>Gibb, Diana, 12</p><p>Girish, Sandhya, 19</p><p>Goldan, Razvan, 11</p><p>Griffiths, Gareth, 8</p><p>Hale, Colin, 8, 13</p><p>Hamani, Naima, 12</p><p>Han, Kelong, 14, 25</p><p>Hanrahan, Kaley, 20</p><p>Hao, Jia, 15</p><p>Hao, Wu, 17–18, 20–21</p><p>Harrington, Conn, 25</p><p>Hassman, Howard, 15</p><p>Hawkes, Jennifer, 23</p><p>Herriott, Joanne, 3</p><p>Hindman, Jason, 19</p><p>Hobson, James, 3</p><p>Ho","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16208","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of down‐titration and discontinuation of heart failure pharmacotherapy in older people: A systematic review and meta‐analysis","authors":"Mai H. Duong, Danijela Gnjidic, Andrew J. McLachlan, Mitchell R. Redston, Parag Goyal, Stephanie Mathieson, Sarah N. Hilmer","doi":"10.1111/bcp.16223","DOIUrl":"https://doi.org/10.1111/bcp.16223","url":null,"abstract":"The aim of this study was to investigate whether interventions to discontinue or down‐titrate heart failure (HF) pharmacotherapy are feasible and associated with risks in older people. A systematic review and meta‐analysis were conducted according to PRISMA 2020 guidelines. Electronic databases were searched from inception to 8 March 2023. Randomized controlled trials (RCTs) and observational studies included people with HF, aged ≥50 years and who discontinued or down‐titrated HF pharmacotherapy. Outcomes were feasibility (whether discontinuation or down‐titration of HF pharmacotherapy was sustained at follow‐up) and associated risks (mortality, hospitalization, adverse drug withdrawal effects [ADWE]). Random‐effects meta‐analysis was performed when heterogeneity was not substantial (Higgins <jats:italic>I</jats:italic><jats:sup>2</jats:sup> &lt; 70%). Sub‐analysis by frailty status was conducted. Six RCTs (536 participants) and 27 observational studies (810 499 participants) across six therapeutic classes were included, for 3–260 weeks follow‐up. RCTs were conducted in patients presenting with stable chronic HF. Down‐titrating a renin‐angiotensin system inhibitor (RASI) in patients with chronic kidney disease was 76% more likely than continuation (risk ratio [RR] 1.76, 95% confidence interval [CI] 1.14–2.73), with no difference in mortality (RR 0.64, 95% CI 0.30–1.64). Discontinuation of beta‐blockers were feasible compared to continuation in preserved ejection fraction (RR 1.00, 95% CI 0.68–1.47). Participants were 25% more likely to re‐initiate discontinued diuretics (RR 0.75, 95% CI 0.66–0.86). Digoxin discontinuation was associated with 5.5‐fold risk of hospitalization compared to continuation. Worsening HF was the most common ADWE. One observational study measured frailty but did not report outcomes by frailty status. The appropriateness and associated risks of down‐titrating or discontinuing HF pharmacotherapy in people aged ≥75 years is uncertain. Evaluation of outcomes by frailty status necessitates investigation.","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstracts of the International Workshop on Clinical Pharmacology of HIV, Hepatitis, and other Antiviral Drugs","authors":"","doi":"10.1111/bcp.16207","DOIUrl":"https://doi.org/10.1111/bcp.16207","url":null,"abstract":"&lt;p&gt;&lt;b&gt;1&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;Preclinical pharmacokinetics of novel long-acting tenofovir alafenamide/bictegravir solid injectable in rats&lt;/b&gt;&lt;/p&gt;&lt;p&gt;Usman Arshad&lt;sup&gt;1,2&lt;/sup&gt;, Eleanor Barlow&lt;sup&gt;2,3&lt;/sup&gt;, Helen Cox&lt;sup&gt;1,2&lt;/sup&gt;, Joanne Sharp&lt;sup&gt;1,2&lt;/sup&gt;, Henry Pertinez&lt;sup&gt;1,2&lt;/sup&gt;, Joanne Herriott&lt;sup&gt;1,2&lt;/sup&gt;, Edyta Kijak&lt;sup&gt;1,2&lt;/sup&gt;, Eduardo Gallardo-Toledo&lt;sup&gt;1,2&lt;/sup&gt;, James Hobson&lt;sup&gt;2,3&lt;/sup&gt;, Andrew Dwyer&lt;sup&gt;2,3&lt;/sup&gt;, Jonathan Massam&lt;sup&gt;2,3&lt;/sup&gt;, Paul Curley&lt;sup&gt;1,2&lt;/sup&gt;, Steve Rannard&lt;sup&gt;2,3&lt;/sup&gt; and Andrew Owen&lt;sup&gt;1,2&lt;/sup&gt;&lt;/p&gt;&lt;p&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;i&gt;Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool;&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt;&lt;i&gt;Centre of Excellence in Long-acting Therapeutics (CELT);&lt;/i&gt; &lt;sup&gt;3&lt;/sup&gt;&lt;i&gt;Department of Chemistry, University of Liverpool&lt;/i&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Tenofovir alafenamide (TAF) is a nucleoside reverse transcriptase inhibitor approved for the treatment of HIV in combination with bictegravir (BIC), an integrase strand transfer inhibitor, and emtricitabine. Daily oral treatment and pre-exposure prophylaxis are highly effective when taken as prescribed. However, inadequate adherence to oral products reduces effectiveness. Another integrase inhibitor, cabotegravir, has been demonstrated to be effective in pre-exposure prophylaxis and is available clinically as a long-acting (LA) injectable. This work describes preclinical pharmacology of a novel TAF/BIC LA solid injectable.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Material and methods:&lt;/b&gt; TAF and BIC formulations were manufactured using emulsion-templated freeze-drying and processed into a compressed solid using vacuum compression moulding (VCM). Male Sprague Dawley rats (&lt;i&gt;n&lt;/i&gt; = 4, 250-300 g) were administered a single TAF and single BIC subcutaneous implant (2 × 8 mm) in the scapular region using a 12-G needle. The implant formulations consisted of 70 wt% BIC or TAF and 30 wt% PVA (24 mg of each drug). Plasma samples were collected from the lateral tail vein throughout a 13-week period. Tenofovir (TFV) and BIC concentrations were quantified in plasma using liquid chromatography–tandem mass spectrometry (LC-MS/MS).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Dispersion of formulations in water yielded TAF or BIC particles with 100–250 nm and 700–850 nm z-average diameters, respectively, as measured by dynamic light scattering. TFV plasma concentrations remained above the human C&lt;sub&gt;trough&lt;/sub&gt; for 7 days and calculated parameters were as follows; a C&lt;sub&gt;max&lt;/sub&gt; of 2681 ng/mL, Tmax of 6 h and AUC&lt;sub&gt;0-tlast&lt;/sub&gt; of 59.6 μg.h/mL and T1/2 of 2.1 days. Plasma BIC concentrations exceeded the human oral steady-state C&lt;sub&gt;trough&lt;/sub&gt; within 3 h of administration and remained above this for 84 days (C&lt;sub&gt;max&lt;/sub&gt; of 33 777 ng/mL, T&lt;sub&gt;max&lt;/sub&gt; = 1 day, AUC&lt;sub&gt;0-tlast&lt;/sub&gt; = 17 669 μg.h/mL, T1/2 of 31 days). No behavioural issues were encountered, animals gained weight throughout, and no overt implant-site reactions were observed.&lt;/p&gt;&lt;","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16207","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adverse reactions associated with nivolumab and small molecule antiangiogenic drugs: A pharmacovigilance analysis","authors":"Haiyang Li, Zhaohui Ruan, Yanan Jia, Yuan Zhang, Lingwa Wang, Yifan Yang, Ru Wang, Jugao Fang","doi":"10.1111/bcp.16242","DOIUrl":"https://doi.org/10.1111/bcp.16242","url":null,"abstract":"AimsImmune checkpoint inhibitors, such as nivolumab, combined with small molecule antiangiogenic receptor tyrosine kinase inhibitors (TKIs), present a promising strategy for future immunotherapy. However, combination therapy can lead to specific adverse drug reactions (ADRs) in various clinical settings. Current research on the ADRs associated with combination therapy is limited. Our study aims to assess the safety of combination therapy.MethodsWe extracted ADR reports on combination therapy from the Food and Drug Administration (FDA) Adverse Event Reporting System database, covering the period from the first quarter of 2012 to the third quarter of 2023, and conducted a large‐scale retrospective study. We evaluated ADR risk signals using the reporting odds ratio (ROR) and calculated the Ro/e ratio to compare the differences in the risk of fatal ADRs among various tumour types.ResultsWe comprehensively reported the occurrence of ADRs in pan‐cancer patients undergoing combination therapy. The combination therapy significantly increased the risk of sensitive skin (ROR: 231.43, 95% CI: 55.01–973.72, <jats:italic>P</jats:italic> &lt; .05), metastatic renal cell carcinoma (ROR: 220.71, 95% CI: 28.99–1695.41, <jats:italic>P</jats:italic> &lt; .05) and renal cell carcinoma (ROR: 188.22, 95% CI: 44.24–800.85, <jats:italic>P</jats:italic> &lt; .05). We also compared the differences in ADRs resulting from different small molecule drug combinations, as well as the differences in ADRs among patients with different types of tumours under combination therapy. Furthermore, we analysed the characteristics of patients prone to experiencing fatal ADRs.ConclusionThese results can help enhance understanding of the ADRs commonly associated with combination therapy and assist oncologists in formulating screening protocols.","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apixaban anti-Xa levels in clinical practice: A case report","authors":"Sarah Clark,&nbsp;Juan Luis Alcala-Zermeno","doi":"10.1111/bcp.16247","DOIUrl":"10.1111/bcp.16247","url":null,"abstract":"<p>Apixaban is a widely used direct oral anticoagulant that is recommended over warfarin therapy for many clinical indications. In patients with atrial fibrillation, dose reductions are recommended for patients with advanced age (≥80 years), low weight (≤60 kg) or elevated serum creatinine (≥1.5 mg/dL), but there is no routine laboratory monitoring necessary for long term-use. Furthermore, apixaban dose reductions due to renal dysfunction are not recommended when treating acute venous thromboembolism. Apixaban-calibrated anti-Xa assays are readily available at some medical centres, and they may be of clinical utility in certain circumstances such as in patients with renal insufficiency, medication adherence assessment, periprocedural planning, extremes in body weight and advanced age. Here, we describe the case of an elderly patient with chronic kidney disease taking apixaban for acute pulmonary embolism. The patient had an unanticipated prolonged apixaban half-life, with detectable apixaban-calibrated anti-Xa levels for &gt;10 days after the last administered dose, which delayed a necessary surgical intervention by &gt;1 week. This case is an example of appropriately using apixaban-calibrated anti-Xa levels to guide therapeutic decision making in perioperative planning.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MCF classifier: Estimating, standardizing, and stratifying medicine carbon footprints, at scale","authors":"Haroon Taylor,&nbsp;Shazia Mahamdallie,&nbsp;Matthew Sawyer,&nbsp;Nazneen Rahman","doi":"10.1111/bcp.16229","DOIUrl":"10.1111/bcp.16229","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Healthcare accounts for 5% of global greenhouse gas emissions, with medicines making a sizeable contribution. Product-level medicine emission data is limited, hindering mitigation efforts. To address this, we created Medicine Carbon Footprint (MCF) Classifier, to estimate, standardize, stratify and visualize medicine carbon footprints.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used molecular weight and chemical structure to estimate the process mass intensity and global warming potential of the active pharmaceutical ingredient in small molecule medicines. This allowed us to estimate medicine carbon footprints per dose, which we categorized into MCF Ratings, accessible via a searchable web application, MCF Formulary. We performed comparison and sensitivity analyses to validate the ratings, and stratification analyses by therapeutic indication to identify priority areas for emission reduction interventions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We generated standardized medicine carbon footprints for 2214 products, with 38% rated LOW, 35% MEDIUM, 25% HIGH and 2% VERY HIGH. These products represented 2.2 billion NHS England prescribed doses in January 2023, with a total footprint of 140 000 tonnes CO₂e, equivalent to the monthly emissions of 940 000 cars. Notably, three antibiotics—amoxicillin, flucloxacillin and penicillin V—contributed 15% of emissions. We estimate that implementing the recommended 20% antibiotic prescription reduction could save 4200 tonnes CO₂e per month, equivalent to removing 29 000 cars.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Standardized medicine carbon footprints have utility in assessing and addressing the carbon emissions of medicines, and the potential to inform and catalyse changes needed to align better healthcare and net zero commitments.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16229","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L‐carnitine for valproic acid‐induced toxicity","authors":"Tomasz Gziut, Ruben Thanacoody","doi":"10.1111/bcp.16233","DOIUrl":"https://doi.org/10.1111/bcp.16233","url":null,"abstract":"AimsReview the effectiveness and dosing of L‐carnitine for valproic‐acid induced toxicity.MethodsA literature review of the pharmacokinetics and clinical use of L‐carnitine was performed.ResultsValproic acid is a fatty acid used for numerous therapeutic indications ranging from epilepsy to bipolar disorder. The metabolism of valproic acid produces both therapeutic and toxic metabolites. Whilst it has a good safety profile, adverse effects of valproic acid in chronic use include hepatotoxicity ranging from transient elevation of liver enzymes to fulminant liver failure and hyperammonaemia with resultant encephalopathy. L‐carnitine is an essential cofactor for mitochondrial fatty acid metabolism, which is an important source of energy in cardiac and skeletal muscle. Physiological concentrations of L‐carnitine are maintained in man by exogenous dietary intake and endogenous synthesis. Following exogenous oral administration of L‐carnitine, the bioavailability ranges from 14% to 18%. After bolus intravenous administration of L‐carnitine in doses ranging from 20 to 100 mg/kg, the volume of distribution is 0.2–0.3 L/kg, and the fraction excreted unchanged in urine is 0.73–0.95, suggesting that renal clearance of L‐carnitine is dose dependent due to saturable renal reabsorption at supraphysiological concentrations.ConclusionsThere is evidence supporting the use of L‐carnitine in treating hyperammonaemia and hepatotoxicity following chronic therapeutic use and after acute overdose of valproic acid, but the optimal dose and route of administration is unknown. Based on the pharmacokinetics of L‐carnitine, we advocate the administration of L‐carnitine for valproic‐acid induced hyperammonaemia or hepatotoxicity as an intravenous loading dose of 5 mg/kg followed by a continuous intravenous infusion instead of the oral or intravenous boluses that are currently advocated.","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142200483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of antidepressants for pain in older adults: A systematic review and meta‐analysis","authors":"Sujita W. Narayan, Vasi Naganathan, Lisa Vizza, Martin Underwood, Rowena Ivers, Andrew J. McLachlan, Linyi Zhou, Ramnik Singh, Shunyu Tao, Xiao Xi, Christina Abdel Shaheed","doi":"10.1111/bcp.16234","DOIUrl":"https://doi.org/10.1111/bcp.16234","url":null,"abstract":"AimsIn many countries, pain is the most common indication for use of antidepressants in older adults. We reviewed the evidence from randomized controlled trials on the efficacy and safety of antidepressants, compared to all alternatives for pain in older adults (aged ≥65 years).MethodsTrials published from inception to 1 February 2024, were retrieved from 13 databases. Two independent reviewers extracted data on study and participant characteristics, primary efficacy (pain scores, converted to 0–100 scale) and harms. Estimates for efficacy were pooled using a random effects model and reported as difference in means and 95% CI. Quality of included trials was assessed using the Cochrane risk of bias tool.ResultsFifteen studies (<jats:italic>n</jats:italic> = 1369 participants) met the inclusion criteria. The most frequently studied antidepressants were duloxetine and amitriptyline (6/15 studies each). Pain related to knee osteoarthritis was the most studied (6/15 studies). For knee osteoarthritis, antidepressants did not provide a statistically significant effect for the immediate term (0–2 weeks), (−5.6, 95% confidence interval [CI]: −11.5 to 0.3), but duloxetine provided a statistically significant, albeit a very small effect in the intermediate term, (≥6 weeks and &lt;12 months), (−9.1, 95% CI: −11.8 to −6.4). Almost half (7/15) of the studies reported increased withdrawal of participants in the antidepressant treatment group <jats:italic>vs</jats:italic>. the comparator group due to adverse events.ConclusionsFor most chronic painful conditions, the benefits and harms of antidepressant medicines are unclear. This evidence is predominantly from trials with sample sizes of &lt;100, have disclosed industry ties and classified as having unclear or high risk of bias.","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142200467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficiency of computerized clinical decision support systems involving anticoagulants: A flashmob study in Dutch hospital pharmacies","authors":"Jetske Graafsma, Ewoudt M. W. van de Garde, Hieronymus J. Derijks, Rien H. L. Hoge, Joanna E. Klopotowska, Fatma Karapinar-Carkit, Patricia M. L. A. van den Bemt","doi":"10.1111/bcp.16236","DOIUrl":"https://doi.org/10.1111/bcp.16236","url":null,"abstract":"Computerized decision support systems (CDSSs) aim to prevent adverse drug events. However, these systems generate an overload of alerts that are not always clinically relevant. Anticoagulants are frequently involved in these alerts. The aim of this study was to investigate the efficiency of CDSS alerts on anticoagulants in Dutch hospital pharmacies.","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142200466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flucloxacillin instantly decreases serum levels of valproic acid: A case report","authors":"Douwe H. van der Meer,&nbsp;Lisa J. Elting,&nbsp;Pleun S. van Egmond","doi":"10.1111/bcp.16244","DOIUrl":"10.1111/bcp.16244","url":null,"abstract":"<p>Valproic acid (VPA) is used for epilepsy and bipolar disorder. It has near-complete bioavailability and is primarily metabolized by glucuronosyltransferases and mitochondrial oxidation. This case highlights a 79-year-old male with bipolar disorder on VPA therapy that started with flucloxacillin for <i>Staphylococcus aureus</i> bacteraemia and exhibited significantly reduced VPA serum levels. During hospitalization, flucloxacillin treatment correlated with a sharp decline of 75% in VPA total serum levels, a novel drug–drug interaction not previously reported. Nonadherence and absorption issues of VPA were ruled out, confirming flucloxacillin's role in reducing VPA levels. Because free-fraction serum levels of VPA remained within therapeutic range (5–25 mg/L) and our patient's bipolar disorder remained stable at 1000 mg twice daily, a dose increase was not necessary. Previous reports described cytochrome P450 enzyme induction as the mechanism of flucloxacillin lowering serum levels of immunosuppressants and antimycotics. Because only 10% of VPA is metabolized by cytochrome P450 enzymes, this is not plausible for this case. The proposed mechanism for the VPA–flucloxacillin drug–drug interaction is flucloxacillin as inducer of glucuronosyltransferase enzymes via the pregnane X receptor pathway, accelerating VPA metabolism. Because this case showed that free-fraction serum levels remained within therapeutic range, it underscores the need for free-fraction VPA monitoring in bipolar disorder and flucloxacillin therapy. When VPA is used for epilepsy, it is advised to consider alternative antibiotics to avoid this interaction.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142200485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}