British journal of clinical pharmacology最新文献

{"title":"Trends in utilization of tramadol and other opioids in Denmark 2017–2023: A nationwide drug utilization study","authors":"Lotte Rasmussen,&nbsp;Martin Thomsen Ernst,&nbsp;Solveig Forberg,&nbsp;Anton Pottegård,&nbsp;Jens Søndergaard,&nbsp;Anne Mette Skov Sørensen","doi":"10.1111/bcp.16360","DOIUrl":"10.1111/bcp.16360","url":null,"abstract":"<p>The use of tramadol and other opioids for pain management has been accompanied by a multitude of challenges and concerns worldwide. The use of tramadol saw a decline in Denmark during 2017–2019 accompanied by a slight increase in the use of morphine and oxycodone. Using the Danish National Prescription Registry and utilizing data until and including 2023, we aimed to provide updated data on the utilization patterns of tramadol and other opioids in Denmark. We found a 35% decline in the use of tramadol from 2017 to 2023 most likely due to media attention, regulatory actions, health campaigns and targeted education of physicians and patients by the Danish health authorities. This decline was accompanied by an increase in the number of new (+90%) and current users of morphine (+57%), which surpassed those of tramadol, oxycodone and other opioids in 2023.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 3","pages":"908-913"},"PeriodicalIF":3.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000455","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":"Optimizing real-world evidence studies for regulatory decision-making and impact assessment in pharmacovigilance.","authors":"Ignatios Ioakeim-Skoufa, Kerry Atkins, Miguel Ángel Hernández-Rodríguez","doi":"10.1111/bcp.16393","DOIUrl":"https://doi.org/10.1111/bcp.16393","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000451","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":"Gut decontamination in the poisoned patient","authors":"Sophie Gosselin,&nbsp;Lotte C. G. Hoegberg,&nbsp;Robert S. Hoffman","doi":"10.1111/bcp.16379","DOIUrl":"10.1111/bcp.16379","url":null,"abstract":"<p>Poisoning management includes gastrointestinal decontamination strategies to decrease the burden of poison entering the body and change the expected severe toxicity expected to a less toxic, more favourable outcome. Common modalities are orogastric lavage, oral-activated charcoal and whole-bowel irrigation. Endoscopic retrieval and laparotomy are rare options reserved for severe ingestions and body packers. Although supporting data are generally of low quality, gastrointestinal decontamination is likely to improve patient outcome in many situations. Unfortunately, technical limitations and contraindications can explain their infrequent use. Orogastric lavage can be useful for early lethal ingestions, albeit with significant complications such as aspiration and perforation. Activated charcoal cannot adsorb every substance. Usual dosing is 1 g/kg per dose. Whole-bowel irrigation is reserved for charged molecules or substances not adsorbed to activated charcoal but requires intact gut motility. Indications depend on several factors inherent to the ingestion (dose, time, poison) and patient's characteristics. During recent decades, studies of newer pharmaceuticals or modified-release formulations showed that significant amounts of poison, especially pharmacobezoars, persist in the gut hours postingestion, thus are amenable to gastrointestinal decontamination. Improved understanding of gut motility in volunteer studies and overdose showed clinically significant reduction in drug exposure with activated charcoal. The 1-h dogma for gastrointestinal decontamination, especially activated charcoal, is now obsolete. Clinicians must perform a risk assessment for each ingestion to determine the expected benefit at the time of decision-making, choosing the modality to achieve reduction in the toxicity burden while planning for complications or contraindications.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 3","pages":"595-603"},"PeriodicalIF":3.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000450","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":"Carbapenems in the management of valproic acid overdose (MPT-01166-24 R1)","authors":"David N. Juurlink","doi":"10.1111/bcp.16376","DOIUrl":"10.1111/bcp.16376","url":null,"abstract":"<p>Severe valproic acid (VPA) overdose is characterized by coma (sometimes with cerebral oedema), respiratory depression, hypotension and metabolic abnormalities. Traditional management of VPA poisoning has been limited to gastrointestinal decontamination, L-carnitine supplementation and, in severe cases, haemodialysis. Recently, interest has developed in the use of carbapenem antibiotics as an adjunctive therapy in patients with severe VPA poisoning. Carbapenems inhibit acylpeptide hydrolase, the enzyme responsible for reconstituting VPA from VPA-glucuronide, and transiently promote distribution of VPA into erythrocytes. In patients receiving VPA therapeutically, carbapenems lower VPA concentrations abruptly, dramatically, and for a sustained period. This article discusses the possibility of exploiting this pharmacokinetic drug–drug interaction in patients with or at risk of severe VPA poisoning.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 3","pages":"648-653"},"PeriodicalIF":3.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982771","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":"The efficacy of hydroxychloroquine in paediatric chronic immune thrombocytopenia: A retrospective cohort study.","authors":"Jing Liu, Yuelun Zhang, Hongmei Song, Mingsheng Ma, Zhuo Li, Lejia Zhang, Yuqing Song, Zichao Lyu, Yixiu Lu, Juan Xiao","doi":"10.1111/bcp.16389","DOIUrl":"https://doi.org/10.1111/bcp.16389","url":null,"abstract":"<p><strong>Aims: </strong>Research on hydroxychloroquine (HCQ) for children with chronic immune thrombocytopenia (ITP) is limited. The association between antinuclear antibody (ANA) positivity and its efficacy remains unclear.</p><p><strong>Methods: </strong>This retrospective cohort study compared the clinical characteristics of children with chronic ITP who received HCQ with those who did not, as well as patients who responded to HCQ at 3 months with those who did not. Mixed-effects models were performed to assess the effect of HCQ on platelet counts and the association between ANA and its efficacy. Records of HCQ-related side effects were reviewed.</p><p><strong>Results: </strong>A total of 191 children with chronic ITP were included in this study, including 42 patients who received HCQ. At the last follow-up, 69.0% of patients treated with HCQ achieved complete response or response, with a median follow-up time of 56 months (range: 17-146 months), a higher frequency compared to 48.3% of patients who were not treated with HCQ (odds ratio [OR], 2.39; 95% confidence interval [CI], 1.15-4.95). The overall response rates to HCQ were 56.8% (21/37) at 3 months and 40.5% (15/37) at 1 year. HCQ was effective for increasing platelet counts (mean difference: 23.82 × 10⁹/L; 95% CI: 7.44-40.21), but the association between ANA positivity and its efficacy was not found. Side effects were recorded in six patients (14.3%).</p><p><strong>Conclusions: </strong>HCQ was associated with increased platelet counts in chronic ITP children. The baseline ANA level was not found to be associated with the efficacy of HCQ. Side effects of HCQ warrant consideration.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982843","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":"Spotlight commentary: Changes in pharmacokinetics following significant weight loss","authors":"Andrej Belančić,&nbsp;Hesham S. Al-Sallami","doi":"10.1111/bcp.16401","DOIUrl":"10.1111/bcp.16401","url":null,"abstract":"&lt;p&gt;Obesity is associated with detrimental metabolic, mechanical and psychological outcomes, leading to diminished qualify of life and reduced lifespan. Whilst lifestyle modifications, including diet and physical activity, remain essential for managing obesity management, many patients with obesity require additional interventions for effective treatment. These include anti-obesity medicines (e.g., GLP-1 receptor agonists) and/or bariatric surgery.&lt;/p&gt;&lt;p&gt;Research investigating changes in pharmacokinetic (PK) and pharmacodynamic (PD) properties following significant weight loss has predominately focused on patients undergoing bariatric surgery. However, with the increasing availability and efficacy of pharmacological anti-obesity interventions, there is a need to highlight the potential impact of significant weight loss on drug dose requirements. This commentary turns the spotlight to the potential of significant weight loss and subsequent changes in drug dose requirements, associated with non-surgical anti-obesity interventions. Spotlight commentaries were introduced to BJCP in 2019 and aim to ‘identify emerging themes—pulling together related content that has recently been published in the Journal [and] placing this in the context of contemporaneous work in other journals’.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Currently, six medications are approved in several countries for treating non-syndromic obesity as adjuncts to lifestyle modifications: orlistat, phentermine, naltrexone/bupropion, liraglutide, semaglutide and tirzepatide.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Among these, tirzepatide has shown the highest efficacy, achieving a median weight loss of 22.5% in one study; comparable to that of some bariatric surgery approaches.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; In comparison, the GLP-1 receptor agonist semaglutide has been reported to induce a median loss of 15.8%.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Bariatric surgery, however, remains associated with greater weight loss, with rates up to 71%.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Obesity and significant weight loss profoundly influence drug pharmacology. The use of total body weight to adjust drug doses in the obese can potentially result in drug toxicity. Ideal body weight (IBW) and other body size descriptors (e.g., body surface area) have shown to be more cautious alternatives to scale drug doses in the obese. However, an accurate scaler requires understanding of the effect of obesity, and significant weight loss, on drug kinetics. Recent work by Busse et al., published in BJCP, and O'Hanlon et al. has demonstrated the role of obesity and body composition on clearance (CL) and volume of distribution (V) and to a lesser extent gastrointestinal transit time and absorption.&lt;span&gt;&lt;sup&gt;5, 6&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Several studies have described the changes in pharmacokinetics and dose requirements following significant and rapid weight loss in the context of bariatric procedures. For instance, Colin et al. demonstrated that fat-free mass (FFM)-","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 3","pages":"678-680"},"PeriodicalIF":3.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16401","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000454","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":"Performance of the accelerated assessment of the European Medicines Agency.","authors":"Vittorio Del Grosso, Martina Perini, Giorgio Casilli, Enrico Costa, Valentina Boscaro, Gianluca Miglio, Armando A Genazzani","doi":"10.1111/bcp.16385","DOIUrl":"https://doi.org/10.1111/bcp.16385","url":null,"abstract":"<p><strong>Aims: </strong>In Europe, the European Medicines Agency (EMA) has an accelerated pathway to prioritize approval of medicines. Approved drugs are then assessed by Health Technology Assessment (HTA) bodies before being made available to patients. The aim of the study was to evaluate the characteristics of the drugs admitted to the EMA accelerated assessment (AA) and scrutinize the downstream HTA procedures regarding these medicines and the final assessment regarding added therapeutic value (ATV).</p><p><strong>Methods: </strong>Regulatory publicly available documents were scrutinized for all medicines authorized by the EMA between 2019 and 2021 to create a regulatory database. A second database was created by extracting data of the medicines that had requested the EMA accelerated pathway from three national HTA bodies (AIFA, HAS and G-BA).</p><p><strong>Results: </strong>Standard assessments by the EMA had a median of 364 days while AAs were significantly shorter (189 days). Only 12 out of 164 authorized medicines were assessed in this manner. Small chemical entities had a significantly lower chance of being assessed under the AA, while biological and PRIME scheme medicines had a higher chance; AA had a higher chance of leading to authorizations under exceptional circumstances. These 12 products were assessed more quickly compared to other products by HTA bodies, although this did not always lead to decisions of major ATV over alternatives.</p><p><strong>Conclusions: </strong>A minority of medicinal products are assessed under the accelerated pathway. HTA bodies also assess these products more quickly, but do not always perceive an important clinical advantage over alternatives.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945045","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":"Common pitfalls in oncology drug applications aiming for conditional marketing authorization","authors":"Sinan B. Sarac,&nbsp;Peter Kiely,&nbsp;Simona Stankeviciute,&nbsp;Jorge Camarero,&nbsp;Amy McKee","doi":"10.1111/bcp.16383","DOIUrl":"10.1111/bcp.16383","url":null,"abstract":"<p>Early approval mechanisms, such as conditional approval in the EU, have been used extensively to provide timely access to therapeutic innovations to cancer patients with unmet medical needs.</p><p>While based on promising early evidence, such approvals are challenging from many perspectives due to the lack of comprehensive data. The limitation typically relates to data that demonstrates clinical benefit via early endpoints and is only acceptable when the early evidence is particularly convincing to assume that the benefits of early access are greater than the potential harms.</p><p>This paper describes the requirements for conditional approval and presents common pitfalls in oncology, such as misunderstandings about the strength of evidence from exploratory trials and secondary analyses, lack of planning and opportunities to improve communication. Thereafter, we present a framework (‘EDGE’) on how to improve the submission and evaluation of drug applications for conditional approval in the EU.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 3","pages":"672-677"},"PeriodicalIF":3.1,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16383","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945042","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":"Unravelling sources of variability on rocuronium pharmacokinetics: Implications for prolonged recovery in older patients.","authors":"Miriam S R Happ, Leandro F Pippa, Gabriela R Lauretti, Anthony R Gebhart, Günther Weindl, Francine J Azeredo, Valvanera Vozmediano, Stephan Schmidt, Natalia V de Moraes","doi":"10.1111/bcp.16386","DOIUrl":"https://doi.org/10.1111/bcp.16386","url":null,"abstract":"<p><strong>Aims: </strong>Residual neuromuscular blockade (RNB) commonly occurs when using neuromuscular blockers and increases the risk for pulmonary complications, such as airway obstruction and severe hypoxemia, in extubated patients. Rocuronium exhibits a high variability in recovery time, contributing to an increased risk for RNB. This study aimed to identify and characterize the sources of variability in rocuronium exposure and response via a population pharmacokinetic/pharmacodynamic (PK/PD) analysis and to apply the developed PK/PD model to investigate clinical implications.</p><p><strong>Methods: </strong>A nonlinear mixed-effect model was developed for rocuronium in patients undergoing general anaesthesia, using doses of 0.3-1.2 mg/kg. Plasma concentrations and the neuromuscular block (train of four ratio) were assessed up to 6 h after dosing. The influence of age, body mass index, renal function and sex on PK and PD was explored. Simulations were performed to predict the recovery time.</p><p><strong>Results: </strong>A two-compartment model with linear elimination and an indirect sigmoid I-max model was used to describe PK and PD. The transfer rate into the periphery increases with age. The predicted recovery time was significantly longer in older subjects aged 85 years (median: 2.8 h; interquartile range [IQR]: 2.18-4.0) compared to young adults aged 25 years (median: 2.5 h; IQR: 2.0-3.1) following single bolus administrations of doses ≥ 0.7 mg/kg.</p><p><strong>Conclusions: </strong>Our findings suggest that older patients take slightly longer to recover than younger adults due to an age-dependent increase in tissue uptake. However, a priori dose adjustments for rocuronium in older patients are not feasible, since age contribution is overshadowed by the overall variability in the recovery time.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945047","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":"Infliximab-induced symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) in a patient with ulcerative colitis","authors":"Mislav Mokos,&nbsp;Vedrana Bulat,&nbsp;Robert Likić,&nbsp;Filip Bosnić,&nbsp;Slavko Gašparov","doi":"10.1111/bcp.16390","DOIUrl":"10.1111/bcp.16390","url":null,"abstract":"<p>Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a rare, symmetrical skin eruption triggered by various medications, predominantly beta-lactam antibiotics. We report the case of a 69-year-old male with moderate-to-severe ulcerative colitis who developed SDRIFE following the seventh intravenous administration of infliximab. The patient presented with symmetrical, pruritic erythema in the cubital and popliteal fossae, groins, gluteal and retroauricular regions without systemic involvement. Skin biopsy showed mild exocytosis of T lymphocytes in the epidermis and dense superficial perivascular CD3+ and CD4+ infiltration, consistent with a type IVa hypersensitivity reaction. The patient responded well to a regimen of systemic antihistamines, topical corticosteroids and tacrolimus ointment, with complete regression of lesions within one week. Despite mild recurrences of SDRIFE after each infliximab administration, the therapy was not discontinued due to the mild nature of the reaction and favourable prognosis. The authors are not aware of previously published cases of type IVa SDRIFE induced by infliximab. Unlike previous reports of severe type IVc SDRIFE reactions requiring discontinuation of infliximab, our case highlights the predominance of CD4+ cells, which may explain the mild clinical course. Understanding the underlying immunologic mechanisms of infliximab-induced SDRIFE could affect treatment decisions and prevent unnecessary discontinuation of effective therapies.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 3","pages":"903-907"},"PeriodicalIF":3.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945043","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}