British journal of clinical pharmacology最新文献

{"title":"Towards greener prescribing? Swedish general practitioners' support for policies to reduce pharmaceutical pollution.","authors":"Johanna Villén, Johanna Laux, Björn Wettermark, Sofia Kälvemark Sporrong, Marmar Nekoro, Helle Håkonsen","doi":"10.1002/bcp.70066","DOIUrl":"https://doi.org/10.1002/bcp.70066","url":null,"abstract":"<p><strong>Aims: </strong>Prescribing pharmaceuticals is essential to improve health, but it also has substantial environmental impact. This study investigated the extent to which Swedish general practitioners (GPs) are willing to integrate environmental aspects into treatment decisions and their opinions on policies to reduce pharmaceutical pollution.</p><p><strong>Methods: </strong>A questionnaire assessing environmental considerations in prescribing was developed and distributed to 1233 Swedish GPs and physicians in training (response rate: 22%) between September 2023 and June 2024. It included 3 patient cases to assess trade-offs between therapeutic effect and environmental impact of pharmaceuticals used for pain management, blood pressure reduction, and contraception. Questions about attitudes to policies to reduce the environmental impact of pharmaceuticals were also included. Data were analysed using descriptive and inferential statistics.</p><p><strong>Results: </strong>Most respondents were willing to prescribe a less effective pharmaceutical if it was environmentally preferable, 77% for pain management and blood pressure reduction, and 50% for contraception. Environmental impact was ranked as the least important factor in prescribing decisions when compared to cost, regional treatment guidelines, dosage intervals, and user-friendliness. A total of 68% of respondents agreed that physicians should consider environmental aspects when prescribing, however only a few often searched for environmental information when prescribing. Policies directed towards other stakeholders, such as authorities and the pharmaceutical industry, received substantial support.</p><p><strong>Conclusion: </strong>Swedish GPs are willing to consider environmental factors when prescribing. However, other factors are more often considered and GPs attribute higher responsibility to other actors. Improving access to environmental information about pharmaceuticals could support greener prescribing.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965978","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":"Implementation of mass pharmacogenetic testing: Dihydropyrimidine dehydrogenase testing prior to fluoropyrimidine treatment for patients.","authors":"Nisha Shaunak, Jessica Keen, Anna Kim, Munir Pirmohamed, William G Newman, Paul J Ross","doi":"10.1002/bcp.70057","DOIUrl":"https://doi.org/10.1002/bcp.70057","url":null,"abstract":"<p><strong>Aims: </strong>Pharmacogenomics enables personalization of drug therapy improving effectiveness and/or safety. Dihydropyrimidine dehydrogenase [DPYD] testing prior to fluoropyrimidine chemotherapy was commissioned by NHS England in response to an update from the Medicines and Healthcare products Regulatory Agency.</p><p><strong>Methods: </strong>A questionnaire developed and approved by the National DPYD Working Group investigated processes of testing, receiving and responding to results. The survey was distributed to Genomics Medicine Service Alliance (GMSA) Clinical Directors and Pharmacy Senior Responsible Officers for dissemination in their geography. Data were collected June-September 2021. All hospitals delivering fluoropyrimidines across the UK were invited to participate.</p><p><strong>Results: </strong>131/138 (94.9%) organizations reported testing all patients receiving fluoropyrimidines. In England 76.7% of hospitals sent samples to centrally commissioned genomics laboratories. In the devolved nations, 73.9% sent samples to regional genomics laboratories. Multidisciplinary staff including oncologists, independent non-medical prescribers, clinical nurse specialists, screening pharmacists and chemotherapy nurses requested the test, checked and actioned the result. Self-reported turnaround times varied from <2 days where a regional laboratory was colocated with a chemotherapy centre to >10 days.</p><p><strong>Conclusion: </strong>Through multiprofessional, national collaboration, this is the first report studying the large-scale rollout of a nationally commissioned pharmacogenetic test. Whilst DPYD testing has been successfully implemented, there is a need to standardize and improve end-to-end turnaround times. This has led to the development of a best practice pathway. Critically, GMSAs must build on this implementation to deliver its priorities, in supporting equitable access to future pharmacogenomic testing across a wider cohort of therapies.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954587","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":"Propafenone- vs. amiodarone-associated adverse cardiac outcomes in patients with atrial fibrillation and heart failure.","authors":"Yi-Cheng Lin, Bi-Li Chen, Chien-Yi Hsu, Li-Ying Chen, Shing-Jong Lin, Gregory Y H Lip, Li-Nien Chien, Chun-Yao Huang","doi":"10.1002/bcp.70068","DOIUrl":"10.1002/bcp.70068","url":null,"abstract":"<p><strong>Aims: </strong>Clinical trials have shown an increased risk of death in patients with recent myocardial infarction who received antiarrhythmic drugs such as flecainide, encainide or moricizine, especially in the presence of associated structural heart disease such as cardiac dysfunction. This study aimed to evaluate the safety outcomes of propafenone use in atrial fibrillation patients with heart failure when compared to those of amiodarone use.</p><p><strong>Methods: </strong>This population-based cohort study used the National Health Insurance Research Database in Taiwan. Eligible patients were those who had atrial fibrillation or atrial flutter diagnosis, had heart failure diagnosis, and first received propafenone or amiodarone between 2002 and 2018. The primary endpoints were death due to arrhythmia and the composite proarrhythmic outcome, which consisted of sudden cardiac arrest, arrhythmic death, ventricular arrhythmia and implantation of defibrillator.</p><p><strong>Results: </strong>After propensity score matching, the study cohort consisted of 7235 propafenone and 14 470 amiodarone users. Compared to amiodarone, propafenone was associated with significantly lower risk of the composite proarrhythmic outcome (adjusted hazard ratio: 0.52; 95% confidence interval: 0.42-0.64; P < .001). Propafenone users also had lower risk of death owing to arrhythmia compared to amiodarone users (adjusted hazard ratio: 0.22; 95% confidence interval: 0.08-0.65; P = .006). Subgroup analysis and sensitivity analysis showed similar trends, favouring propafenone.</p><p><strong>Conclusion: </strong>Propafenone was not significantly associated with increased risk of proarrhythmia and mortality when compared to amiodarone in atrial fibrillation patients with heart failure in contemporary real-world settings. Prospective studies are needed to determine whether propafenone should definitely be avoided in these patients.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983106","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":"Effectiveness and safety of long-term therapy with alirocumab in acute coronary syndrome patients: A single-centre retrospective real-world study.","authors":"Linghua Chen, Mengshuang Li, Yecheng Deng, Ziqiu Chen, Rufeng Huang, Xin Yang, Zhaoqi Huang","doi":"10.1002/bcp.70072","DOIUrl":"https://doi.org/10.1002/bcp.70072","url":null,"abstract":"<p><strong>Aims: </strong>Although guidelines recommend in-hospital initiation of high-intensity statin therapy in patients with acute coronary syndromes (ACS), low-density lipoprotein cholesterol (LDL-C) target levels are frequently not attained. Alirocumab has been demonstrated to be a fast-acting and efficacious agent for lowering LDL-C in controlled trials. However, there is a paucity of real-world evidence concerning its use in patients of Chinese ethnicity with ACS. This real-world observational study aimed to assess the efficacy and safety of alirocumab in Chinese ACS patients.</p><p><strong>Methods: </strong>This study is a single-centre, retrospective study involving 73 patients with ACS treated with alirocumab over 6 months, followed up at 1, 3, 6 and 12 months, the main observation measure is the achieved rate of LDL-C levels after treatment with alirocumab at 6 months.</p><p><strong>Results: </strong>In comparison with baseline, alirocumab therapy for 6 months was associated with a significant increase in percentage of patients who attained the control goal of LDL-C <1.0 mmol/L (51.3 vs. 1.4%, P < .0001) and <1.4 mmol/L (61.5 vs. 5.5%, P < .0001), respectively.</p><p><strong>Conclusion: </strong>There was a significant reduction in LDL-C levels with alirocumab with or without lipid-lowering therapy treatment in ACS patients in this real-world evidence study. The percentage of patients achieving LDL-C goals of <1.00 and <1.40 mmol/L were significantly higher than baseline 6 months after the adding alirocumab.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989101","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":"Metamizole induces voriconazole metabolism and results in subtherapeutic voriconazole concentrations.","authors":"Simone D Baan, Daan J Touw, Marjolijn N Lub-de Hooge, Thijs H Oude Munnink","doi":"10.1002/bcp.70079","DOIUrl":"https://doi.org/10.1002/bcp.70079","url":null,"abstract":"<p><strong>Aims: </strong>Voriconazole is extensively metabolized via cytochrome P450 (CYP) enzymes, predominantly CYP2C19 and CYP3A4. Drugs influencing the activity or expression of CYP enzymes can cause clinically relevant changes in the metabolism and voriconazole exposure. Metamizole is known to induce CYP3A4 and CYP2C19. This study aimed to investigate the pharmacokinetic drug-drug interaction between metamizole and voriconazole.</p><p><strong>Methods: </strong>In this single-centre retrospective observational cohort study, we compared voriconazole serum trough concentrations before, during and after metamizole treatment.</p><p><strong>Results: </strong>In the 9 included patients, the median voriconazole trough concentration decreased by 71% during metamizole treatment (P = .028) compared to before start of metamizole. The concentration/dose ratio similarly decreased by 81% during metamizole treatment (P = .018). Additionally, the metabolic ratio (voriconazole-n-oxide/voriconazole) increased from 0.9 to 2.4 (P = .028) during metamizole treatment. Subtherapeutic voriconazole trough concentrations were more frequent when combined with metamizole (before 14%, during 70%, after 17%).</p><p><strong>Conclusions: </strong>Metamizole increases voriconazole metabolism and decreases voriconazole trough concentrations, probably through a CYP3A4 and CYP2C19 inducing effect. It is recommended to avoid concurrent use of metamizole and voriconazole or to closely monitor voriconazole trough concentrations during metamizole treatment and up to 2 weeks after discontinuation of metamizole.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954352","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":"Appraising the visibility, relevance and impacts of clinical pharmacology","authors":"Serge Cremers,&nbsp;Samuel L. M. Arnold,&nbsp;Nilima A. Kshirsagar,&nbsp;Catriona Waitt,&nbsp;Olayinka O. Ogunleye,&nbsp;Lars L. Gustafsson","doi":"10.1002/bcp.70074","DOIUrl":"10.1002/bcp.70074","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Clinical pharmacology (CP) used to be a strong medical and scientific field, but during the last three decades it seems to have lost some of its appeal. We reviewed the visibility, relevance and impact of CP and clinical pharmacologists across the globe and suggest ways to strengthen the discipline to address future pharmacotherapeutic challenges.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Literature consultations and multiple survey approaches through personal contacts with leading experts from high-income countries, Asia and Africa and with CP scientific journal editors with presentation, discussion and recommendations at a workshop (World Congress in Basic and Clinical Pharmacology, Glasgow 2023).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Historically, CP has been a leading discipline for the advancement of knowledge and practice of rational principles for human drug use. However, currently there is variable visibility and impact between countries in research, education and clinical services. The workshop participants agreed that CP continues to be an open transdisciplinary subject to address challenges of drug development with affordable access to essential medicines and rational use of new advanced therapies as well as essential medicines. Medical specialisation programmes in clinical pharmacology and therapeutics should be the norm and become attractive through introducing board programmes for accreditation of specialists building on models existing in some European countries, India, Nigeria and South Africa.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Clinical pharmacologists should collaborate across countries and disseminate success stories, demonstrating their essential contributions to medical science and patient care. A <i>white book</i> with comprehensive global representation on the future role, structure and impact of the discipline should be developed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 7","pages":"1884-1898"},"PeriodicalIF":3.1,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bcp.70074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966255","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 pharmacokinetic analysis of the interaction of digoxin with N-desethylamiodarone in patients with atrial fibrillation and heart failure.","authors":"Toshinori Hirai, Hidefumi Kasai, Tsuyoshi Shiga","doi":"10.1002/bcp.70075","DOIUrl":"https://doi.org/10.1002/bcp.70075","url":null,"abstract":"<p><strong>Aims: </strong>To evaluate the effects of amiodarone and/or N-desethylamiodarone concentrations on digoxin pharmacokinetics and determine the optimal dose of digoxin combined with amiodarone in Japanese patients with atrial fibrillation and heart failure.</p><p><strong>Methods: </strong>A population pharmacokinetic analysis of 3288 points from 368 patients receiving oral digoxin, including 48 (13%) who were coadministered amiodarone, was performed. A 1-compartment model with first-order absorption with amiodarone or N-desethylamiodarone as time-varying covariates for apparent digoxin clearance was constructed using stepwise forward inclusion and backward elimination approaches. The percentage of patients with digoxin values in the toxic range (≥0.9 ng/mL) was evaluated with Monte Carlo simulation.</p><p><strong>Results: </strong>The median serum digoxin concentration was 0.75 ng/mL; the median plasma concentrations of amiodarone and N-desethylamiodarone were 610 and 644 ng/mL, respectively. The final model for oral clearance of digoxin was explained by creatinine clearance (CLcr) and the N-desethylamiodarone concentration. Digoxin clearance increased by 21% when CLcr was doubled and decreased by 3% when the N-desethylamiodarone concentration increased by 100 ng/mL. In the simulation, the proportion of patients with values in the toxic range was high at 0.125 mg daily among patients taking amiodarone. A daily dose of 0.0625 mg is recommended for patients with a CLcr >30 mL/min. For patients with a CLcr ≤30 mL/min and an N-desethylamiodarone concentration >600 ng/mL, a daily dose of 0.03125 mg is recommended because of reduced digoxin clearance.</p><p><strong>Conclusions: </strong>This study revealed that renal impairment and high plasma N-desethylamiodarone concentrations reduce digoxin clearance in patients with atrial fibrillation and heart failure.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966237","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":"A novel approach for first-in-human dose selection using population dose-response modelling to find a minimum anticipated biological effect level.","authors":"Lin Yuan, Meghana Kulkarni, Evan Chiswick, Cheryl Koh, Peter Sandy, Salah Nabhan, Woody Sherman, Melissa Johnson, Judy Wang, Gerald Falchook, Jennifer Johnson, Christopher Winter, Humphrey Gardner, Arijit Chakravarty, Madison Stoddard","doi":"10.1002/bcp.70067","DOIUrl":"https://doi.org/10.1002/bcp.70067","url":null,"abstract":"<p><strong>Aims: </strong>Choice of first-in-human dose has critical implications for the safety of Phase I participants as well as the likelihood of reaching the therapeutic dose range during escalation. In this analysis, we present a population concentration-response modelling approach for selecting the Phase I starting dose for a novel stimulator of interferon response cGAMP interactor 1 (STING) agonist, SNX281.</p><p><strong>Methods: </strong>Given the immune agonist mechanism of SNX281, we opted to select the starting dose according to the minimum anticipated biological effect level (MABEL). To determine the MABEL concentration, we fitted a population concentration-response model to cytokine induction data from an ex vivo whole blood assay. We selected a whole blood assay to obviate the need for free fraction scaling for this highly protein-bound drug. We used the population concentration-response model to estimate the lower 10th percentile for the 10% maximal interferon-β response concentration of SNX281, which was chosen as the MABEL concentration. We translated the ex vivo MABEL concentration to a human MABEL dose using a human pharmacokinetic projection based on allometric scaling from preclinical species.</p><p><strong>Results: </strong>The human dose-peak concentration relationship projection fell within 2-fold of the clinical result. After the application of a safety factor, the MABEL dose was applied in the clinic and did not demonstrate dose-limiting toxicities.</p><p><strong>Conclusions: </strong>Our novel population modelling-based MABEL strategy for first-in-human dose selection resulted in successful clinical translation of a small molecule STING agonist.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959298","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: De-labelling the truth: Clearing the fog around antibiotic allergy labels.","authors":"Iva Mikulić, Robert Likić","doi":"10.1002/bcp.70085","DOIUrl":"https://doi.org/10.1002/bcp.70085","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"e70085"},"PeriodicalIF":3.1,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980779","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":"A phase 1, randomized, crossover trial to assess the effect of itraconazole on the pharmacokinetics of dordaviprone in healthy adults.","authors":"Shamia L Faison, Joelle Batonga, Thangam Arumugham, Angela Bartkus, Marion E Morrison, Mark J Mullin, Tim Tippin, Odin Naderer","doi":"10.1002/bcp.70080","DOIUrl":"https://doi.org/10.1002/bcp.70080","url":null,"abstract":"<p><strong>Aims: </strong>Dordaviprone (ONC201) is a novel, small molecule with antitumor efficacy in gliomas. The aim of this work was to evaluate the pharmacokinetics and safety of dordaviprone when given alone and when coadministered with a strong cytochrome P450 (CYP)3A4 inhibitor, itraconazole.</p><p><strong>Methods: </strong>In vitro human liver microsomes and recombinant human CYP enzyme assays were used to assess CYP-mediated metabolism of dordaviprone. The clinical study was conducted in 18 healthy male and female participants as part of a larger 3 period open-label, randomized, crossover bioequivalence and drug-drug interaction evaluation. Dordaviprone and metabolite ONC207 plasma concentrations were determined by validated liquid chromatography-tandem mass spectrometry methods.</p><p><strong>Results: </strong>In vitro assessments of CYP-mediated dordaviprone metabolism indicated that CYP3A4 was the major CYP involved in the oxidation of dordaviprone. Accordingly, concomitant administration of dordaviprone with itraconazole significantly increased dordaviprone plasma maximum plasma concentration and area under the plasma concentration-time curve by 1.9 and 4.5-fold, respectively, compared to dordaviprone alone. Treatment-emergent adverse events were reported by 1 (5.6%) participant after receiving dordaviprone alone, and by 4 (22.2%) participants after receiving dordaviprone with itraconazole.</p><p><strong>Conclusion: </strong>Concomitant administration of dordaviprone with itraconazole significantly increased dordaviprone exposure confirming CYP3A4 is a major clearance pathway for dordaviprone. While dordaviprone was generally well tolerated when administered as a single 125-mg dose with concomitant itraconazole, dose adjustment in patients receiving 625 mg dordaviprone with strong CYP3A4 inhibitors is warranted.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976704","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}