British journal of clinical pharmacology最新文献

{"title":"Understanding factors that influence the drug choice of prescribers: A Q-methodology study.","authors":"Mariëlle G Hartjes, Annelot E F Elsevier, Jan Willem Grijpma, Milan C Richir, Michiel A van Agtmael, Jelle Tichelaar","doi":"10.1002/bcp.70009","DOIUrl":"https://doi.org/10.1002/bcp.70009","url":null,"abstract":"<p><strong>Introduction: </strong>Therapeutic decision-making often involves weighing several treatment options on the basis of, among other things, the disease profile, patient characteristics but also prescriber-specific factors. This study investigated the factors influencing therapeutic decision-making among prescribers and explores how these factors differ between healthcare professionals.</p><p><strong>Methods: </strong>This Q-methodology study involved 37 participants from different medical backgrounds, including physicians, dentists, midwives, physician assistants and advanced nurse practitioners from various intra- and extramural settings in the Netherlands. Participants ranked 55 factors on their importance for medication prescribing, and factor analysis was used to identify distinct prescriber profiles. These profiles were subsequently enriched using qualitative data derived from post-sorting interviews.</p><p><strong>Results: </strong>Four prescriber profiles were identified that explained 59% of the study variance: pragmatic contextual, guideline oriented, experience driven and vulnerability focused. Several factors were ranked differently in each profile. The pragmatic contextual profile emphasized patient context and risk prevention, the guideline-oriented profile adhered to clinical guidelines, the experience-driven profile relied on clinical experience and patient-centred communication, and the vulnerability-focused profile prioritized personalized care for specific patient groups.</p><p><strong>Conclusion: </strong>This study sheds light on the diverse factors influencing prescriber decision-making in medical practice. By identifying four prescriber profiles, it reveals the complexity and diversity in how prescribers balance guidelines, clinical experience and patient-specific considerations in their practice. These findings offer direction for developing educational and policy initiatives to enhance the quality of prescribing, ultimately improving patient outcomes.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490810","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":"Assessment of ethnic differences in pharmacokinetics and clinical responses of acalabrutinib between Chinese and White patients with B-cell malignancies.","authors":"Tingting Yao, Junjie Ding, Shringi Sharma, Yunfei Li, Qianwei Xu, Peiming Ma","doi":"10.1002/bcp.70018","DOIUrl":"https://doi.org/10.1002/bcp.70018","url":null,"abstract":"<p><strong>Aims: </strong>The aim of this study was to assess differences between Chinese and White patients in pharmacokinetics (PK) of, and clinical response to, acalabrutinib and its pharmacologically active major metabolite, ACP-5862, to support recommended dosing in Chinese patients with B-cell malignancies.</p><p><strong>Methods: </strong>A population pharmacokinetic (pop-PK) analysis was conducted to integrate data from a Chinese and a Japanese study into the existing model. The effect of race (East Asian vs. non-East Asian) on acalabrutinib and ACP-5862 PK parameters was assessed. The relationships between model-predicted exposures (e.g., acalabrutinib area under the plasma concentration-time curve for 24 h at steady-state [AUC_24h,ss]) and best overall response and safety outcomes were investigated in Chinese patients and the overall population.</p><p><strong>Results: </strong>The pop-PK analysis included 686 patients with B-cell malignancies (Chinese, n = 105; Japanese, n = 6). A two-compartment model adequately described the PK profiles of acalabrutinib and ACP-5862 for Chinese patients. East Asian race was a statistically significant covariate on relative bioavailability and apparent volume of the peripheral compartment of acalabrutinib, showing 28% higher PK exposures in Chinese patients. The exposure-efficacy analysis showed that efficacy plateaued in Chinese patients with 100 mg twice-daily dosing while the exposure-safety analysis indicated a flat relationship of acalabrutinib AUC_24h,ss with grade ≥2 or ≥3 adverse events in both Chinese patients and the overall population with 100-400 mg daily doses.</p><p><strong>Conclusions: </strong>Higher PK exposure was observed in Chinese patients vs. White patients but did not indicate a safety concern based on exposure-response relationships. The results supported using the 100 mg twice-daily dosing regimen in Chinese patients.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490807","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":"Prescriptions of CYP3A4- and P-gp inducers for patients on direct oral anticoagulants: Bridging the gap between epidemiology and patient management for optimal thromboembolic event prevention.","authors":"Stephanie C M Wuyts, Joris De Moor, Kristin Jochmans, Pieter-Jan Cortoos, Fenne Vandervorst, Stephane Steurbaut, Alain G Dupont, Pieter Cornu","doi":"10.1002/bcp.70007","DOIUrl":"https://doi.org/10.1002/bcp.70007","url":null,"abstract":"<p><p>Direct oral anticoagulants (DOACs) are frequently used for the treatment and prevention of ischaemic stroke in patients with non-valvular atrial fibrillation. Compared to vitamin K antagonists, DOACs have significant advantages, although their drug-drug interaction (DDI) profile may complicate drug efficacy and safety. This narrative review addresses the clinical challenges posed by these DDIs and the potential pharmacological alternatives and monitoring strategies available. A PubMed search was conducted (1 January 2000-31 December 2023) including human DDI studies on DOAC use and CYP3A4/P-gp inducers in adult patients, evaluating patient outcome data and recommendations for DDI management. Twenty-two studies were included. Case reports (n = 6) indicated that antiepileptic drugs such as carbamazepine, phenobarbital and phenytoin may be associated with thromboembolic events. The nested case-control studies (n = 2) and cohort studies (n = 9) found that co-administration of DOACs and CYP3A4/P-gp inducers, particularly carbamazepine and phenytoin, increased the risk of thromboembolic events. Pharmacovigilance database analyses indicated a significant association between DOAC DDIs and increased reported stroke rates. Management recommendations in systematic reviews (n = 5) highlighted monitoring when DOACs were combined with inducers. Strategies included using alternative drugs with a weaker or preferentially absent inducing profile. Limited evidence suggests that edoxaban may be an acceptable option in case of DOAC and CYP3A4/P-gp inducer interactions; however, robust clinical data confirming safety are needed. Present literature indicates a higher thromboembolic risk in patients on DOAC treatment combining CYP3A4- and/or P-gp inducers. DOAC management should be tailored to the individual patient through collaboration between expert healthcare professionals.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490809","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":"Effect of hydration schedules on dose-limiting toxicity in patients with head and neck squamous cell carcinoma treated with cisplatin.","authors":"Anouk W M A Schaeffers, Cassimy B van Neerven, Dorieke van Balen, Mirjam Crul, Marije Slingerland, Saskia A C Luelmo, Jan Paul de Boer, Jens Voortman, Arjan D van Zuilen, Remco de Bree, Lot A Devriese","doi":"10.1002/bcp.70015","DOIUrl":"https://doi.org/10.1002/bcp.70015","url":null,"abstract":"<p><strong>Aims: </strong>The aim of this study was to determine if head and neck squamous cell carcinoma (HNSCC) patients treated with cisplatin chemoradiotherapy and short hydration (SH) experience less dose-limiting toxicity (DLT) and receive more cisplatin than those with medium hydration (MH) or long hydration (LH).</p><p><strong>Methods: </strong>Baseline characteristics, cumulative cisplatin dose and toxicities were collected. Differences between LH, MH and SH were tested, with separate analyses for triweekly 100 mg/m² cisplatin and weekly 40 mg/m² cisplatin. Mixed models assessed the hydration schedule's effect on cumulative dose.</p><p><strong>Results: </strong>A total of 389 patients were included. DLT occurrence was comparable between hydration groups (P = .060), but DLT type differed (P = .007). Nephrotoxicity was common with LH and MH (n = 11, 61% and n = 26, 45%, respectively), and ototoxicity with SH (n = 35, 36%). DLT occurrence in triweekly patients differed between LH and MH (n = 18, 64% vs n = 25, 32%, P = .004), but not between MH and SH (P = .171) or LH and SH (P = .055) patients. Cisplatin dose differed between LH and MH (median 200 vs 300, P = .008) as well as between LH and SH (median 200 vs 300, P = .024) but not between MH and SH (P = .429) patients. Hydration had no effect on dose (F = 2.09, P = .125).</p><p><strong>Conclusions: </strong>DLT cause differed between hydration groups, with less nephrotoxicity but more ototoxicity in HNSCC patients with SH. Triweekly cisplatin LH patients had more DLT and lower cumulative dose compared to MH and SH, but no hydration effect in general on dose was found.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482238","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":"Investigation of a broad-spectrum micronutrient formulation as a possible precipitant of pharmacokinetic micronutrient-drug interactions.","authors":"Bess M Kew, Matthew P Doogue, Richard McNeill, Mei Zhang, Julia J Rucklidge, Christopher M Frampton, Roger T Mulder, Ben Beaglehole","doi":"10.1002/bcp.70014","DOIUrl":"https://doi.org/10.1002/bcp.70014","url":null,"abstract":"<p><strong>Aims: </strong>Daily broad-spectrum micronutrients are being used by the general public and formulations are receiving research interest in mental health settings. Despite concerns about combining medicines and broad-spectrum micronutrients in mental health care, there have not been any formal evaluations of potential interactions. Our objective was to evaluate a broad-spectrum micronutrient formula as a potential precipitant of pharmacokinetic drug-drug interactions through inhibition or induction of cytochrome P450 (CYP) enzymes.</p><p><strong>Methods: </strong>This was a single-centre pharmacokinetic study. Twelve healthy participants received broad-spectrum micronutrients for 14 days (Days 1-14). Participants were administered a 'cocktail' of selective CYP probes midazolam 2 mg (CYP3A), dextromethorphan 30 mg (CYP2D6), losartan 25 mg (CYP2C9), omeprazole 20 mg (CYP2CI9) and caffeine 100 mg (CYP1A2) on Day 0 and Day 14, before taking and while taking broad-spectrum micronutrients. Plasma drug concentrations were measured at baseline and for 8 h following cocktail administration. AUC, C_max and T_max were compared before and after broad spectrum micronutrient administration using paired t-tests.</p><p><strong>Results: </strong>Pre- and post-micronutrient geometric means (SD) for AUC_0-8h (μg*h/L) were: midazolam 25 (13) and 26 (14), P = 0.60; dextromethorphan 25 (99) and 19 (110), P = 0.46; losartan 219 (105) and 205 (76), P = 0.20; omeprazole 474 (394) and 402 (342), P = 016; and caffeine 13 800 (5400) and 12 800 (3500), P = 0.79. There were no statistically significant changes in geometric means of probe C_max, or T_max for any of the study drugs.</p><p><strong>Conclusions: </strong>Broad-spectrum micronutrients are unlikely to be a major precipitant of pharmacokinetic drug-drug interactions.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490808","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":"Letter to the editor concerning the article: 'The impacts of undetected nonadherence in phase II, III and post-marketing clinical trials: An overview'.","authors":"Tamás Ágh, Lina Eliasson, Bijan Borah","doi":"10.1002/bcp.70030","DOIUrl":"https://doi.org/10.1002/bcp.70030","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482173","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":"Feasibility and population exposure of 5-fluorouracil using therapeutic drug monitoring (PREDICT-5FU): A multicentre clinical trial.","authors":"Sarah Glewis, Michael Michael, Howard Gurney, Ian Olver, Nicholas Zdenkowski, Stephen Ackland, Craig Kukard, Madawa Jayawardana, S Sandun M Silva, Marliese Alexander, Jeanne Tie, Peter Galettis, Jennifer H Martin","doi":"10.1002/bcp.70006","DOIUrl":"https://doi.org/10.1002/bcp.70006","url":null,"abstract":"<p><strong>Aim: </strong>PREDICT-5FU aimed to document 5-fluorouracil (5FU) exposure in a cancer population and to evaluate the feasibility of 5FU and capecitabine therapeutic drug monitoring (TDM) in patients receiving standard doses and schedules.</p><p><strong>Methods: </strong>Multicentre, prospective, observational single-arm study. Eligible adult patients received 5FU (infusional ≥24 h) or capecitabine. Patients were treated for gastrointestinal, breast and head-and-neck cancers at four Australian hospitals. TDM was performed in consecutive cycles until target area under the curve (AUC) was reached. Pharmacogenetic testing was performed for all patients.</p><p><strong>Results: </strong>Fifty patients (24 males, 26 females) were recruited. Median age was 63 years; common diagnoses were lower gastrointestinal cancers 40% (20/50) and metastatic disease 80% (40/50). The majority received 5FU (38/50, 76%) over 46 h. Only 36% of 5FU patients achieved target AUC when dosed based on body surface area; 61% were below and 3% above target range. Post TDM-adjusted dosing, target AUC was achieved in 58% of patients (22% absolute increase vs. BSA dosing, p = 0.03), within median three cycles (range 1-5). DPYD variant allele carriers (3/4) had upfront reduced dosing due to heterozygosity; all were below the target AUC and one experienced Grade 3 toxicity. There was no correlation between dihydrouracil: uracil ratio [UH2/U] or uracilemia [U] and DPYD genotype. TDM results were reported with an average of 4 days from sampling.</p><p><strong>Conclusion: </strong>TDM dosing is feasible and increases the proportion of patients reaching target AUC. Findings are relevant across all cancers treated with 5FU, and particularly for DPYD variant allele carriers receiving upfront dose reductions.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482162","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 cardiovascular effects associated with the use of prescription medications: A Danish nationwide screening study.","authors":"Saad Hanif Abbasi, Lars Christian Lund, Jesper Hallas, Martin Thomsen Ernst, Anton Pottegård","doi":"10.1002/bcp.16406","DOIUrl":"https://doi.org/10.1002/bcp.16406","url":null,"abstract":"<p><strong>Aim: </strong>This study aims to conduct a hypothesis-generating screening for acute cardiovascular effects of prescription medications.</p><p><strong>Methods: </strong>This Danish nationwide screening study was conducted among incident cases of cardiovascular diseases, including myocardial infarction (MI), ischemic stroke (IS), heart failure (HF), venous thromboembolism (VTE), myocarditis, and atrial fibrillation (AF), between January 2000 and December 2022. Using a case-crossover study design, we examined exposure to individual drugs on the date of the cardiovascular event (focal date) and three reference dates corresponding to days -180, -270 and -360 prior to index date. We calculated odds ratios (ORs) with 95% credible intervals (CIs) for associations between exposure drug and cardiovascular outcomes using the conditional logistic regression with a weak Bayesian shrinkage.</p><p><strong>Results: </strong>After applying exclusion criteria, we identified 191,979 cases of AF, 145,148 cases of MI, 132,271 cases of IS, 71,821 cases of HF, 16,127 cases of VTE and 10,045 cases of myocarditis. Based on the threshold for the strength of associations (OR ≥ 1.5; lower limit of CI ≥ 1), we identified 222 associations for 104 individual drugs across all six outcomes. Some major drug classes, such as antibiotics, analgesics and corticosteroids, consistently demonstrated associations for most cardiovascular outcomes. Use of pantoprazole, in contrast to other PPIs, was associated with AF (OR 1.83; 95% CI 1.68-2.00) along with MI, HF, myocarditis and VTE. Similarly, oxazepam stood out among other benzodiazepines and demonstrated increased risk of VTE (OR 2.53; 95% CI 1.55-4.13) as well as MI, HF and AF.</p><p><strong>Conclusions: </strong>The results highlight several potentially important associations across various pharmacological drug classes that warrant further investigation in tailored pharmacoepidemiological analyses.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466979","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":"Investigating started sample size, completed sample size and drop-out rate in 10 252 phase III clinical trials: Insights from ClinicalTrials.gov.","authors":"Henian Chen, Jinyong Pang, Yayi Zhao, Biwei Cao, Matthew J Valente, Weiliang Cen, Elena Valkanova","doi":"10.1002/bcp.70023","DOIUrl":"https://doi.org/10.1002/bcp.70023","url":null,"abstract":"<p><strong>Aims: </strong>This study investigated the started sample size, completed sample size and drop-out rate of 10 252 published and unpublished phase III clinical trials registered on ClinicalTrials.gov over the past 20 years.</p><p><strong>Methods: </strong>We conducted a comprehensive search on ClinicalTrials.gov for all phase III clinical trials with registered results before 26 May 2023. We retrieved and downloaded 10 252, which covered a period of more than 20 years.</p><p><strong>Results: </strong>Out of the 10 252 trials analysed, 889 (8.7%) were sponsored by the US National Institutes of Health/US Federal agencies (NIH/US Fed), 8429 (82.2%) were sponsored by industry. The overall median started sample size was 302. The overall median completed sample size was 228. The median completed sample sizes were 258 for industry-sponsored trials, and 194 for NIH/US Fed-sponsored trials. The median completed sample sizes were 321 for biological interventions and 223 for drug interventions. The overall median drop-out rate was 11%. Statistically significant differences were observed in sample sizes between industry-sponsored trials and NIH/US Fed-sponsored trials (P < 0.0001). Neither the started sample sizes nor the completed sample sizes have shown any change over the course of the past 20 years.</p><p><strong>Conclusions: </strong>Our findings indicate that a majority of the analysed trials lack sufficient statistical power (80%) to detect small effect sizes, and approximately half of the trials did not have 80% power to detect medium effect sizes. Notably, trials funded by NIH/US Fed exhibit significantly smaller sample sizes compared to trials sponsored by industry. When conducting sample size calculations for clinical trials, it is crucial to consider the anticipated effect size, variability and drop-out rate.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466981","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":"Population pharmacokinetics and dosing of dispersible moxifloxacin formulation in children with rifampicin-resistant tuberculosis.","authors":"Megan Palmer, Yuanxi Zou, Anneke C Hesseling, Louvina van der Laan, Ingrid Courtney, Aarti A Kinikar, Naresh Sonkawade, Mandar Paradkar, Vandana Kulkarni, Dessa Jean O Casalme, Melchor V G Frias, Heather Draper, Lubbe Wiesner, Mats O Karlsson, Paolo Denti, Elin M Svensson, Anthony J Garcia-Prats","doi":"10.1002/bcp.70005","DOIUrl":"https://doi.org/10.1002/bcp.70005","url":null,"abstract":"<p><strong>Aims: </strong>Moxifloxacin is a priority drug for treating rifampicin-resistant tuberculosis (RR-TB). We assessed the pharmacokinetics of a child-friendly, dispersible 100 mg tablet moxifloxacin formulation (dispersed in water) compared to the standard 400 mg non-dispersible formulation (crushed and suspended in water) in children and evaluated current dosing recommendations.</p><p><strong>Methods: </strong>The CATALYST trial investigated the pharmacokinetics of moxifloxacin in children with RR-TB. Children were enrolled in South Africa, India and the Philippines. Intensive pharmacokinetic sampling was undertaken while children were taking the standard non-dispersible 400 mg moxifloxacin tablet formulation and repeated after switching to the novel dispersible formulation. Pharmacokinetic data were analysed using population pharmacokinetic modelling. Simulations were performed to evaluate moxifloxacin exposures in children compared to consensus adult reference exposures using current World Health Organization (WHO)-recommended doses and more recent model-based doses.</p><p><strong>Results: </strong>Thirty-six children were enrolled [median age 4.8 (range 0.4-15) years and weight 15.6 (range 6.9-42.1) kg]. A two-compartment disposition model with first-order elimination and delayed absorption was developed. The bioavailability of dispersible versus standard formulations fulfilled standard bioequivalence criterion (ratio 1.05 with 90% confidence interval 0.95-1.15). Simulations showed WHO-recommended doses achieved exposures similar to those in adults in children >10 kg, while children <10 kg may require 33%-56% higher doses to reach adult reference exposures.</p><p><strong>Conclusions: </strong>Dosing recommendations for children can be the same for the dispersible paediatric and standard non-dispersible adult moxifloxacin formulation. The current WHO dosing recommendation risks underdosing moxifloxacin in children <10 kg. We propose optimized moxifloxacin doses for both formulations.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432512","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}