British journal of clinical pharmacology最新文献

{"title":"Adaptive dosing of high-dose busulfan in real-world adult patients undergoing haematopoietic cell transplant conditioning.","authors":"Dorian Protzenko, Benjamin Bouchacourt, Laure Carriat, Paul Maroselli, Clara Boéri, Raynier Devillier, Joseph Ciccolini","doi":"10.1111/bcp.16343","DOIUrl":"https://doi.org/10.1111/bcp.16343","url":null,"abstract":"<p><strong>Aim: </strong>To evaluate the effectiveness of a Bayesian adaptive dosing strategy in achieving target busulfan exposure in adult patients undergoing haematopoietic cell transplantation (HCT).</p><p><strong>Methods: </strong>This study included 71 adult patients scheduled to receive high-dose busulfan. Busulfan was administered to achieve a cumulative area under the curve (AUC) of 66.0 mg/L/h (16 000 μM/min), 82.60 mg/L/h (20 000 μM/min) or 87.6 mg/L/h (21 200 μM/min) depending on the regimen. Individual pharmacokinetic (PK) parameters of busulfan were estimated from three blood samples using a one-compartment model and Bayesian estimation after the first standard dose. Individual PK parameters were used to adjust subsequent doses to achieve the target exposure.</p><p><strong>Results: </strong>All patients had their dose adjusted after the first dose administration. The final deviation from the target AUC was significantly improved compared to the initial deviation after standard mg/kg dosing (mean absolute deviation 19.5% vs 11.7%, P < .01). In addition, the proportion of patients with marked deviation from target exposure (ie, >25%) decreased significantly from 31% after standard dosing to 10% after PK-guided dosing (P < .01). Canonical busulfan-related toxicity, specifically veno-occlusive disease, was observed in 5% of patients who achieved successful PK-guided dosing. In contrast, one-third of patients with off-target exposure with poor dosing experienced toxicity.</p><p><strong>Conclusion: </strong>The Bayesian adaptive dosing strategy significantly improves the accuracy of achieving the target busulfan AUC in patients undergoing HCT. This approach not only reduces marked deviations from target exposure, but also reduces the incidence of busulfan-related toxicity, thereby maintaining a favourable toxicity/efficacy ratio.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675184","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":"Impact of treosulfan exposure on clinical outcome after allogeneic stem cell transplantation in children: A substudy of 2 phase 2 trials","authors":"Krzysztof Kalwak,&nbsp;Ajay Vora,&nbsp;Peter Bader,&nbsp;Birgit Burkhardt,&nbsp;Selim Corbacioglu,&nbsp;Katarzyna Drabko,&nbsp;Jolanta Gozdzik,&nbsp;Johann Greil,&nbsp;Bernd Gruhn,&nbsp;Katharine Patrick,&nbsp;Ansgar Schulz,&nbsp;Petr Sedlacek,&nbsp;Jan Styczynski,&nbsp;Monika Mielcarek-Siedziuk,&nbsp;Franco Locatelli,&nbsp;Dirk Reinhardt,&nbsp;Paul-Gerhardt Schlegel,&nbsp;Joachim Baumgart,&nbsp;Jochen Kehne,&nbsp;Xieran Li,&nbsp;Rita Beier","doi":"10.1111/bcp.16339","DOIUrl":"10.1111/bcp.16339","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a vital treatment for various paediatric malignant and nonmalignant diseases. The conditioning treatment before allo-HSCT is crucial for successful engraftment. Treosulfan, a cytotoxic prodrug, has gained popularity due to its lower toxicity compared to traditional alkylating agents used for conditioning treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We investigated the relationship between pharmacokinetics and pharmacodynamics of treosulfan in paediatric patients, in a substudy pooling from 2 multicentre phase 2 clinical trials. A total of 83 children with malignant and nonmalignant diseases received treosulfan-based conditioning. Treosulfan exposure and its relationship with clinical outcomes, including survival, graft failure and graft-<i>vs</i>.-host disease, were investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings reveal no significant association between treosulfan exposure and the key clinical outcomes or toxicity (<i>P</i>-values between .22 and .99), if the dosing is based on the approved product information.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that treosulfan exposure after standardized body surface area-based dosing is appropriate in paediatric allo-HSCT.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 3","pages":"882-893"},"PeriodicalIF":3.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675196","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":"Pharmacogenomics in 2023: Big studies, big results, big implications, big responsibilities: Editorial","authors":"Ann K. Daly,&nbsp;Andrew A. Somogyi","doi":"10.1111/bcp.16351","DOIUrl":"10.1111/bcp.16351","url":null,"abstract":"&lt;p&gt;This themed issue is concerned with recent developments in pharmacogenomics and originates from the 19th IUPHAR World Congress of Basic and Clinical Pharmacology 2023 (WCP2023) event in Glasgow, Scotland, where a well-attended symposium featured presentations from Masaru Koido (Japan), Volker Lauschke (Germany and Sweden) and Erika Cecchin (Italy), all early career scientists with rising reputations in the field. These speakers have provided invited review articles for this issue.&lt;/p&gt;&lt;p&gt;The term pharmacogenomics now encompasses the area of pharmacogenetics, which had its origins in the 1950s&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; and developed subsequently as an important branch of clinical pharmacology. &lt;i&gt;British Journal of Clinical Pharmacology&lt;/i&gt; has been a major contributor to publications of key research in this field since the 1970s and 1980s when some of the initial reports on the debrisoquine polymorphism and the later identification of CYP2D6 as the relevant enzyme involved appeared.&lt;span&gt;&lt;sup&gt;2, 3&lt;/sup&gt;&lt;/span&gt; Follow-up studies on the relevance of &lt;i&gt;CYP2D6&lt;/i&gt; phenotype and genotype to metabolism of drugs such as beta-adrenoreceptor antagonists and opioids subsequently appeared in the journal&lt;span&gt;&lt;sup&gt;4-6&lt;/sup&gt;&lt;/span&gt; with coverage also extending to other highly polymorphic P450s of clinical pharmacology importance such as &lt;i&gt;CYP2C9&lt;/i&gt; and &lt;i&gt;CYP2C19&lt;/i&gt;.&lt;span&gt;&lt;sup&gt;7, 8&lt;/sup&gt;&lt;/span&gt; In spite of the extensive knowledge and understanding achieved in this field during the 50 years of &lt;i&gt;British Journal of Clinical Pharmacology&lt;/i&gt;,&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; clinical implementation of pharmacogenomics is still limited. However, appreciation of the importance of personalized prescribing based on patient genotype is now widespread, as reported recently by Turner and colleagues who reviewed a joint report from Royal College of Physicians and British Pharmacological Society on using pharmacogenomics to improve patient outcomes.&lt;span&gt;&lt;sup&gt;10&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;In parallel with development of pharmacogenomics, population studies worldwide, including the UK Biobank, FinnGen and All of Us, feature extremely large sample sizes while parallel developments in genomics in relation to performing and analysing whole genome sequencing as well as the availability of complementary ‘omics’ data such as serum proteomics now provide a huge amount of data. Dealing with these data will require use of approaches such as Machine Learning (ML), but this should further increase pharmacogenomics knowledge and facilitate personalized prescribing.&lt;/p&gt;&lt;p&gt;In this issue, Tremmel and colleagues&lt;span&gt;&lt;sup&gt;11&lt;/sup&gt;&lt;/span&gt; discuss the challenges that still exist in genome sequencing, especially in relation to some pharmacogenes such as CYP2D6. They also consider the range of bioinformatic tools that can be applied to sequencing data to extract pharmacogenomic data and use of artificial intelligence (AI) and ML to predict pharmacological effects and potentially therapeutic response (","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 2","pages":"249-251"},"PeriodicalIF":3.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16351","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675110","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":"What can pharmacokinetic modelling do for you? Rational design and interpretation of clinical studies.","authors":"Francis Williams Ojara, Aida N Kawuma, Catriona Waitt","doi":"10.1111/bcp.16341","DOIUrl":"10.1111/bcp.16341","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614479","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":"Acute aseptic meningitis temporally associated with trimethoprim and sulfamethoxazole: Systematic review","authors":"Gianmaria F. Bernasconi,&nbsp;Gregorio P. Milani,&nbsp;Elisabetta L. T. De Felice,&nbsp;Craig Laurence,&nbsp;Pietro B. Faré,&nbsp;Benedetta Terziroli Beretta-Piccoli,&nbsp;Mario G. Bianchetti,&nbsp;Sebastiano A. G. Lava","doi":"10.1111/bcp.16346","DOIUrl":"10.1111/bcp.16346","url":null,"abstract":"<p>Sulphonamides and trimethoprim, although generally well-tolerated, have been temporally associated with aseptic meningitis. To address its presentation and outcome, a literature search was performed. We retained articles reporting patients with features of acute aseptic meningitis following intake of trimethoprim, sulfamethoxazole or sulfisoxazole. A cerebrospinal fluid investigation in ≥1 episode was a prerequisite for inclusion. Sixty articles reporting on 74 patients experiencing a total of 155 episodes were retained. Forty-five (61%) patients had one or more recurrences. Median age at first episode was 43 (interquartile range [IQR] 23–61) years. Symptoms presented within 48 (IQR 6–168) hours of intake at the first episode and within 1.3 (IQR 1–5) hours at recurrences (<i>p</i> &lt; .0001). Cerebrospinal fluid analysis revealed a predominantly neutrophilic (82%, IQR 65%–94%) pleocytosis (180, IQR 38–507 10⁶ cells/L), without low glucose or high proteins. Recovery took place within 2 (IQR 1–3) days after stopping the suspected agent. All but one patient completely recovered.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 1","pages":"236-243"},"PeriodicalIF":3.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614398","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":"Ten-year analgesic utilization patterns and economic implications in Portugal","authors":"Nuno Duarte,&nbsp;João Paulo Martins,&nbsp;Jose-Ángel García-Pedraza,&nbsp;Marlene Santos","doi":"10.1111/bcp.16333","DOIUrl":"10.1111/bcp.16333","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study evaluated the 10-year consumption and economic patterns of classical analgesics, adjuvants and opioids in Portugal (2012-2022), and conducted a comparative analysis between Portugal, Spain and Denmark to explore the consumption patterns among these countries for 2022.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data on sales and national health service (NHS) costs were obtained from the Portuguese National Authority of Medicines and Health Products. Sales data were converted to defined daily dose (DDD) per 1000 inhabitants per day according to the Anatomical Therapeutic Chemical (ATC) classification/DDD methodology, while comparisons between Spain and Denmark were evaluated with the chi-square test, when appropriate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The findings reveal that classical analgesics use in Portugal remained stable during the period 2012-2022, with ibuprofen being the most consumed. Adjuvants, specifically gabapentinoids, experienced an 84% increase in use, primarily attributed to pregabalin. Weak opioids, led by tramadol, witnessed a 117% rise in use, while strong opioid use, led by tapentadol, increased by 618%. Portugal presented the lowest overall opioid consumption when compared to Denmark and Spain in 2022. Economic trends indicated a heightened NHS expenditure on analgesics, primarily driven by increased opioid use. Notwithstanding, there was no significant burden on relative expenditure over the 10-year period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Portugal presented a major increase in both weak and strong opioid prescriptions, aligning with the trends for Spain and Denmark. The development and approval of generic medicines and vigilant market monitoring are imperative strategies for managing the escalated costs resulting from heightened consumption, particularly concerning opioids.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 3","pages":"866-881"},"PeriodicalIF":3.1,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16333","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614421","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":"External evaluation of intravenous vancomycin population pharmacokinetic models in adults receiving high-flux intermittent haemodialysis","authors":"Cheng Ji,&nbsp;Jonathan Garcia,&nbsp;Argem Joy Sabuga,&nbsp;Maurane Ricard,&nbsp;France Dion,&nbsp;Vlad Alexandru Rosu,&nbsp;Marie-Ève Legris,&nbsp;Amélie Marsot,&nbsp;Van Dong Nguyen","doi":"10.1111/bcp.16334","DOIUrl":"10.1111/bcp.16334","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Patients undergoing haemodialysis (HD) are at greater risk of methicillin-resistant <i>Staphylococcus aureus</i> infections requiring intravenous vancomycin. Close vancomycin therapeutic drug monitoring is warranted in HD patients as renal clearance is the primary elimination pathway. Clinically, population pharmacokinetics (popPK) model-informed dosing is commonly used. This study aimed to perform an external evaluation of published vancomycin popPK models developed for adults undergoing high-flux intermittent HD, and to create a dosing nomogram derived from the model that performed best.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A literature review was conducted through PubMed and EMBASE to identify relevant popPK models. an external dataset was collected retrospectively from patients of 2 healthcare centres in Quebec, Canada. Selected models were implemented in <i>NONMEM</i> (v7.5; ICON Development Solutions). Predictive performance was assessed through prediction and simulation-based diagnostics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 2386 vancomycin concentrations were collected from 274 patients and 476 antibiotic courses. Four vancomycin popPK models were selected for evaluation. None of the models demonstrated overall satisfactory or clinically acceptable predictive performance. Nonetheless, Bae et al.’s model performed best with a median prediction error of 16.25% and median absolute prediction error of 34.66%. Different predictive performance was also observed for vancomycin concentrations from samples collected during and between HD sessions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>All evaluated models presented poor overall predictive performance. Further studies are required, through existing popPK model parameter re-estimation or new model development, to adequately describe vancomycin pharmacokinetics for our high-flux intermittent HD patient cohort.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 3","pages":"856-865"},"PeriodicalIF":3.1,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16334","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614403","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":"Population pharmacokinetics and exposure–response relationships of dostarlimab in primary advanced or recurrent endometrial cancer in part 1 of RUBY","authors":"Mita Kuchimanchi,&nbsp;Trine Lembrecht Jørgensen,&nbsp;Eva Hanze,&nbsp;Thierry André,&nbsp;Angela Jain,&nbsp;Dominique Berton,&nbsp;Oskar Alskär,&nbsp;Oleksandr Zub,&nbsp;Ana Oaknin,&nbsp;Mark S. Shahin,&nbsp;Anthoula Koliadi,&nbsp;Bhavana Pothuri,&nbsp;Tom Krivak,&nbsp;Mikalai Pishchyk,&nbsp;Yakir Segev,&nbsp;Floor J. Backes,&nbsp;Christine Gennigens,&nbsp;Sara Bouberhan,&nbsp;Stefan Zajic,&nbsp;Murad Melhem,&nbsp;Joseph Buscema","doi":"10.1111/bcp.16325","DOIUrl":"10.1111/bcp.16325","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Dostarlimab-gxly is a humanized monoclonal antibody of the IgG4 isotype that binds to the programmed cell death protein-1 (PD-1) receptor and blocks its ligands. RUBY (NCT03981796) is a two-part multicentre study in patients with recurrent or primary advanced endometrial cancer. The overall aims were to characterise the population pharmacokinetics (PopPK) from Part 1 of this study, identify relevant covariates of interest, and assess exposure–efficacy/safety (ER) relationships.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A PopPK model developed using GARNET (NCT02715284) study data for dostarlimab monotherapy was externally validated with RUBY Part 1 study data. Subsequently, the model was updated with data across the two studies. Exposure–safety analyses for adverse events related to dostarlimab alone or in combination with standard of care (SOC) were modelled using logistic regression. Exposure–efficacy analysis included Cox proportional hazards analysis of the primary efficacy endpoint of progression-free survival (PFS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>For the model update, 7957 pharmacokinetics observations from 868 patients pooled from both RUBY and GARNET studies were available. The model was consistent with the previous model. Dostarlimab clearance was estimated to be 7.79% lower when dostarlimab was given as SOC combination therapy. However, no significant covariates were clinically relevant. Hepatic or renal impairment did not affect pharmacokinetics. Among the safety endpoints, only rash showed a small yet statistically significant effect (<i>P</i> &lt; .05) in all subjects; however, this was not not deemed clinically relevant. There were no other clinically significant exposure–safety or exposure–PFS relationships.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The addition of chemotherapy to dostarlimab had limited effect on dostarlimab PopPK, with no clinically significant covariates or clinically relevant exposure–safety or exposure–PFS relationships.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 3","pages":"841-855"},"PeriodicalIF":3.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16325","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614404","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":"SLCO1B1 variants in a patient of African ancestry presenting with rosuvastatin-induced rhabdomyolysis: A case report","authors":"Samantha Medwid,&nbsp;Rowan Deckert,&nbsp;Steven E. Gryn,&nbsp;Richard B. Kim","doi":"10.1111/bcp.16329","DOIUrl":"10.1111/bcp.16329","url":null,"abstract":"<p>We report a case of an adult woman of African ancestry who was hospitalized with statin induced- rhabdomyolysis. The patient presented to the emergency room with a 2-week history of worsening muscle pain, nausea, vomiting and low oral intake, 1 month after starting 40 mg daily dose of rosuvastatin. Sequencing of <i>SLCO1B1</i> coding regions revealed the patient was heterozygous for two <i>SLCO1B1</i> deleterious variants, c.481+1G&gt;T and c.1463G&gt;C (*9), which are more prevalent in patients of African ancestry. This highlights the importance of pharmacogenetic testing in <i>SLCO1B1</i>, which includes a broader range of genetic variants for patients of African ancestry.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 1","pages":"232-235"},"PeriodicalIF":3.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603339","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":"Physicians' and pharmacists' perspective on clarity and clinical relevance of absolute contraindications in “Summaries of Product Characteristics”","authors":"Wahram Andrikyan,&nbsp;Michael I. Sponfeldner,&nbsp;Lea Jung-Poppe,&nbsp;Pauline Dürr,&nbsp;Melanie I. Straubmeier,&nbsp;Anna K. Schuster,&nbsp;Laura Weisbach,&nbsp;Katrin Farker,&nbsp;Michael Hartmann,&nbsp;Martin F. Fromm,&nbsp;Renke Maas","doi":"10.1111/bcp.16331","DOIUrl":"10.1111/bcp.16331","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Previous work has identified several limitations in “Summaries of Product Characteristics” (SmPCs), which are associated with risks for patients. The aim of this study was to evaluate pharmacists' and physicians' interpretation of contraindications in SmPCs and reasons for their nonadherence in clinical routine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>For 20 commonly missed or ignored absolute contraindications, an anonymous online survey providing 24 clinical example cases (one or two per contraindication) for physicians and pharmacists was developed. Experts in medication safety were asked whether the respective case fulfilled the definition of the contraindication in the SmPC: (a) formally, irrespective of the clinical relevance of the contraindication (17 cases), and (b) whether the contraindication was deemed clinically relevant in each respective case (24 cases).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-seven pharmacists and 27 physicians completed the survey. For only one case (1/17; 5.8%) did all experts agree on the same answer option regarding the formal fulfilment of a given contraindication statement. Experts gave heterogeneous answers regarding the interpretation of a contraindication. For instance, among 10 predefined answer options for the contraindication “active liver disease” in the SmPC of simvastatin, every option was selected by at least six experts. In 17/24 (70.8%) clinical example cases a majority of experts agreed on the clinical relevance of a given contraindication. Key reasons for nonadherence to contraindications were “patient monitoring possible”, “lack of alternative treatment” and “acute/severe situations”.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Experts' disagreement on the interpretation of contraindications in SmPCs using clinical example cases indicates that further efforts are needed to improve their usability in clinical routine.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 3","pages":"829-840"},"PeriodicalIF":3.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16331","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603432","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}