British journal of clinical pharmacology最新文献

{"title":"The pharmacokinetics of brensocatib in participants with renal impairment following a single oral administration.","authors":"Sam Au Yeung, Daniel S Stein, Thomas C Marbury, Helen Usansky","doi":"10.1111/bcp.16344","DOIUrl":"https://doi.org/10.1111/bcp.16344","url":null,"abstract":"<p><strong>Aim: </strong>Brensocatib is an oral, selective, competitive and reversible dipeptidyl peptidase 1 inhibitor in development for the treatment of bronchiectasis. This study evaluated the pharmacokinetics (PKs), safety and tolerability of brensocatib in participants with varying degrees of renal impairment and normal renal function.</p><p><strong>Methods: </strong>In this phase 1, multicentre, open-label study, 28 participants with mild, moderate or severe renal impairment (estimated glomerular filtration rate [eGFR] 60 to <90, 30 to <60 and 15 to <30 mL/min/1.73 m², respectively) or normal renal function (≥90 mL/min/1.73 m²) received a single oral 25-mg dose of brensocatib. Blood samples were collected to measure brensocatib PKs at predetermined time points over the 14-day study period. PK parameters were derived using noncompartmental methods.</p><p><strong>Results: </strong>Demographic and baseline characteristics were similar across groups. There were no significant differences between groups in brensocatib PK parameters. The mean coefficient of variation (CV) of elimination half-life of brensocatib was 37.0 (15.3), 42.8 (21.7), 36.3 (22.9) and 39.1 (17.8) h for mild, moderate, severe and normal renal function groups, respectively. Single-dose brensocatib was quickly absorbed; all groups had a median time to maximum observed plasma concentration of 1 h. Regression model analyses indicated no significant relationships between selected brensocatib PK parameters and eGFR. No treatment-emergent adverse events were reported during the study.</p><p><strong>Conclusion: </strong>Single-dose brensocatib was well tolerated. The study data do not indicate a significant effect of renal impairment on brensocatib elimination and systemic exposure, suggesting that dose adjustment of brensocatib is not necessary in participants with renal impairment.</p><p><strong>Clinical trial registration number: </strong>NCT05673603.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686185","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":"Recommended approaches for integration of population pharmacokinetic modelling with precision dosing in clinical practice.","authors":"Monika Berezowska, Isaac S Hayden, Andrew M Brandon, Arsenii Zats, Mehzabin Patel, Shelby Barnett, Kayode Ogungbenro, Gareth J Veal, Alaric Taylor, Jugal Suthar","doi":"10.1111/bcp.16335","DOIUrl":"https://doi.org/10.1111/bcp.16335","url":null,"abstract":"<p><p>Current methods of dose determination have contributed to suboptimal and inequitable health outcomes in underrepresented patient populations. The persistent demand to individualise patient treatment, alongside increasing technological feasibility, is leading to a growing adoption of model-informed precision dosing (MIPD) at point of care. Population pharmacokinetic (popPK) modelling is a technique that supports treatment personalisation by characterising drug exposure in diverse patient groups. This publication addresses this important shift in clinical approach, by collating and summarising recommendations from literature. It seeks to provide standardised guidelines on best practices for the development of popPK models and their use in MIPD software tools, ensuring the safeguarding and optimisation of patient outcomes. Moreover, it consolidates guidance from key regulatory and advisory bodies on MIPD software deployment, as well as technical requirements for electronic health record integration. It also considers the future application and clinical impact of machine learning algorithms in popPK and MIPD. Ultimately, this publication aims to facilitate the incorporation of high-quality precision-dosing solutions into standard clinical workflows, thereby enhancing the effectiveness of individualised dose selection at point of care.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680784","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":"Toxicokinetic modelling of the synthetic cannabinoid 5F-MDMB-P7AICA and its main metabolite in pigs following pulmonary administration.","authors":"Adrian A Doerr, Christiane Dings, Omar Zaher, Frederike Nordmeier, Nadja Walle, Matthias W Laschke, Michael D Menger, Peter H Schmidt, Markus R Meyer, Thorsten Lehr, Nadine Schaefer","doi":"10.1111/bcp.16340","DOIUrl":"https://doi.org/10.1111/bcp.16340","url":null,"abstract":"<p><strong>Aims: </strong>Since their emergence on the drug market, synthetic cannabinoids (SC) are still gaining increasing importance in forensic toxicology. The representatives of the so-called new psychoactive substances have in common that they have not undergone preclinical safety studies. Hence, knowledge on toxicokinetic (TK) data is sparse. As an alternative to human studies not being allowed for ethical reasons, a sophisticated pig model was applied in the present study to assess the TK of the SC 5F-MDMB-P7AICA.</p><p><strong>Methods: </strong>Pigs pulmonarily received 5F-MDMB-P7AICA via an ultrasonic nebulizer. The parent compound and its main metabolite 5F-MDMB-P7AICA dimethyl butanoic acid were determined in serum and whole blood using liquid chromatography-tandem mass spectrometry. Obtained data was analysed by population (pop) TK modelling. The final pop TK model parameters for pigs were upscaled via allometric scaling techniques for the prediction of human exposure.</p><p><strong>Results: </strong>The serum concentration-time profiles of the parent and the pop TK analysis revealed that a 4-compartment model best describes the TK data. The administration of the aerosol into the lung compartment follows zero-order kinetics. A transit compartment was further included to accurately describe the time delay between detection of the parent and the metabolite. Despite the different structure, TK parameters were found to be comparable to other examined SC.</p><p><strong>Conclusion: </strong>The predictions of human SC exposure suggest that multiple administration of 5F-MDMB-P7AICA substantially enhances the window of detection. The simulations pose extrapolation of the data used for model development with respect to dose linearity and allometric scaling to humans.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680798","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":"Determination of the optimal obesity-adjusted dosing weight for enoxaparin.","authors":"Gregory W Roberts, Viviane De Menezes Caceres, Anthony Damiani, Nicholas Scarfo, Desmond B Williams, Patrick T Russell","doi":"10.1111/bcp.16338","DOIUrl":"https://doi.org/10.1111/bcp.16338","url":null,"abstract":"<p><strong>Aims: </strong>The ideal dosing weight metric for enoxaparin remains elusive. Dosing remains focused on actual body weight, which may inadvertently increase the risk of bleeding in those with obesity, or ideal weight, which may underdose those with obesity. Our aim was to determine the optimal obesity-adjusted enoxaparin dosing weight.</p><p><strong>Methods: </strong>Multisite retrospective data were collected over a 2.0-year period for those with minimum 48 h of in-hospital twice-daily enoxaparin and factor anti-Xa level 3-5 h postdose (n = 220). Multiple linear regression calculated the associated variance between a range of nominal dosing weights and factor anti-Xa levels, adjusted for renal function. Dosing weights were calculated as ideal body weight (IBW) and then adjusted for increasing percentages of weight above IBW, i.e. IBW + 10% above IBW, IBW + 20% etc. up to actual body weight. A similar approach was used for lean body weight (LBW).</p><p><strong>Results: </strong>For body mass index ≥30 kg/m² optimal variance explained by dosing weight metrics was at IBW + 40% (23%) and similarly for LBW + 40% (23%). Using actual body weight (ABW) had lowest associated variance with factor anti-Xa levels (18%) followed by unadjusted IBW (13%) or unadjusted LBW (19%). In those with body mass index <30 kg/m² there was similar associated variance in the ranges of IBW + 20-50% and LBW 10-40% (21%).</p><p><strong>Conclusion: </strong>Compared to IBW + 40% or LBW + 40% use of ABW to calculate dose was poorly associated with factor anti-Xa levels, as was IBW or LBW. IBW + 40% and LBW + 40% require further study as a dosing weight metric and may provide a more consistent factor anti-Xa response in those with obesity.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680775","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":"Risk factors for lenvatinib-induced hypertension in patients with hepatocellular carcinoma: A retrospective study","authors":"Shusuke Uekusa,&nbsp;Misaki Nakashin,&nbsp;Yuki Hanai,&nbsp;Maho Nemoto,&nbsp;Sachiko Yanagino,&nbsp;Yoshiki Arita,&nbsp;Takahiro Matsumoto,&nbsp;Noritaka Wakui,&nbsp;Hidenari Nagai,&nbsp;Koji Higai,&nbsp;Kazuhiro Matsuo","doi":"10.1111/bcp.16337","DOIUrl":"10.1111/bcp.16337","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Lenvatinib mesylate (LEN) is an orally administered tyrosine kinase inhibitor used to treat various cancers, including hepatocellular carcinoma (HCC). LEN therapy for HCC is associated with a high incidence of adverse events, including hypertension (HTN). However, the risk factors associated with LEN therapy remain unclear. This study investigated the incidence of LEN-induced HTN (LENiHTN), and the relationship between HTN incidence and patient demographics in patients with HCC receiving LEN therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a single-centre, retrospective study of patients with HCC who received LEN therapy between 19 April 2018 and 30 September 2020. The observation period was from 1 week before the start to 1 month after the end of LEN administration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seventy-five patients with HCC were enrolled. Any grade LENiHTN was found in 74.7% of patients. Among patients with LENiHTN, the use of 2 or more antihypertensive agents before starting LEN was less common (<i>P</i> = .007); serum potassium (K) and albumin–bilirubin score (ALBI) were lower (<i>P</i> = .013 and 0.038, respectively); and albumin (Alb) was higher (<i>P</i> = .025). The cut-off values of K, Alb and ALBI for HTN were estimated at 4.1 mEq L⁻¹, 3.1 g dL⁻¹ and −1.736, respectively. In the multivariable analysis, low K (adjusted HR: 2.078) and low ALBI (adjusted HR: 2.845) were independent risk factors for LENiHTN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Low K, high Alb and low ALBI were independent risk factors for LENiHTN. Systematic evaluation of HTN risk and early intervention for HTN prevention among high-risk patients can markedly enhance LEN therapy efficacy and use.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 3","pages":"894-902"},"PeriodicalIF":3.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16337","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680792","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":"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}