Clinical Pharmacokinetics最新文献

{"title":"Optimising Paediatric Medication Adherence Through Innovative Drug Formulations and Delivery Systems.","authors":"Nokwanda Nhlanzeko Ngcobo","doi":"10.1007/s40262-026-01630-8","DOIUrl":"10.1007/s40262-026-01630-8","url":null,"abstract":"<p><p>Medication adherence remains a significant challenge in healthcare, particularly in paediatric populations, where non-adherence has a substantial impact on therapeutic outcomes and contributes to increased healthcare costs. This manuscript emphasises the central role of drug formulations and delivery systems in shaping adherence behaviours in children. Given the unique pharmacokinetic characteristics of paediatric patients, formulation design has a critical impact on medication efficacy, safety and acceptability. By integrating pharmacological considerations with innovative formulation strategies and tailored care approaches, this work provides practical and evidence-informed pathways to enhance medication adherence and improve clinical outcomes in paediatric care.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"515-526"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nomograms for Therapeutic Drug Monitoring of High-Dose Amikacin in Critically Ill Patients: Insights from a Population Pharmacokinetic Analysis and Dosing Simulation.","authors":"Thi Cuc Nguyen, Dinh Van Le, Hoang Anh Nguyen, Nguyen Tran Nam Tien, Thi Hong Ngoc Nguyen, Dinh Hoa Vu, Hoang Anh Nguyen, Hong Nhung Pham, Cong Tan Nguyen, Dang Minh Vuong Nguyen, The Thach Pham, Ngoc Son Do, Quoc Tuan Dang, Xuan Co Dao, Jan-Willem C Alffenaar","doi":"10.1007/s40262-026-01621-9","DOIUrl":"10.1007/s40262-026-01621-9","url":null,"abstract":"<p><strong>Background and objective: </strong>This study evaluated the probability of pharmacokinetic/pharmacodynamic efficacy target attainment and developed a dosing interval identification nomogram to minimize toxicity risks of high-dose amikacin.</p><p><strong>Methods: </strong>Therapeutic drug monitoring was performed in critically ill patients receiving high-dose (30 mg/kg) amikacin intravenously. Population pharmacokinetic modeling and Monte Carlo simulation were performed in NONMEM^® 7.5.1. The probability of target attainment and the cumulative fraction of response for the local Klebsiella pneumoniae population were assessed using maximum concentration/minimum inhibitory concentration ≥ 8 as the efficacy target. Nomograms stratified by the renal function group were established to guide dosing intervals to avoid exceeding the toxicity minimum concentration threshold of 2.5 mg/L.</p><p><strong>Results: </strong>A total of 251 patients with 488 amikacin concentrations were included. The amikacin pharmacokinetics was best described by a two-compartment model. The creatinine clearance and adjusted body weight were significant covariates for clearance and the central volume of distribution, respectively. Amikacin 30 mg/kg achieved a probability of target attainment > 90% for minimum inhibitory concentrations < 8 mg/L and around 80% for minimum inhibitory concentrations of 8 mg/L. This regimen showed a cumulative fraction of response of 63.5% for K. pneumoniae, while attaining a cumulative fraction of response of 96.8% for susceptible isolates. The 30-mg/kg nomograms in patients with creatinine clearance < 60 and ≥ 60 mL/min showed accurate dosing intervals with around 90% of virtual patients for the post-infusion period from 20 to 32 h and from 6 to 32 h, respectively.</p><p><strong>Conclusions: </strong>Nomogram-aided dosing interval adjustment of high-dose amikacin (30 mg/kg) maximized the efficacy and safety target attainment for critically ill patients with infections caused by susceptible K. pneumoniae.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"557-570"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Model‑Based Alternative Dosing Strategies for Subcutaneous Nivolumab to Improve Cost Effectiveness.","authors":"Yan Wang, Laura H Bukkems, Rob Ter Heine, J G C van Hasselt, S L W Koolen, J J M A Hendrikx, Tom Van der Hulle, Ellen Kapiteijn, Juliette Zwaveling, Annemarie Becker, Michel M van den Heuvel, Willemijn S M E Theelen, Thijs H Oude Munnink, Egbert F Smit, Henk-Jan Guchelaar, Dirk Jan A R Moes","doi":"10.1007/s40262-026-01627-3","DOIUrl":"10.1007/s40262-026-01627-3","url":null,"abstract":"","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"633"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation and Improvement of Specialized Vancomycin Pharmacokinetic Models for Pediatric Cardiovascular Intensive Care Unit and Pediatric Oncology Patients.","authors":"Michael G McCarthy, Ron J Keizer, Jasmine H Hughes","doi":"10.1007/s40262-026-01623-7","DOIUrl":"10.1007/s40262-026-01623-7","url":null,"abstract":"<p><strong>Background and objective: </strong>Dose optimization of vancomycin in distinct pediatric subpopulations is inherently complex due to altered vancomycin pharmacokinetics associated with certain conditions or circumstances, such as cancer or postoperative cardiac surgery. Numerous population pharmacokinetic models have been developed that aim to capture these alterations; however, it is currently unclear whether these specialized models are necessary, or if covariates in a well-specified general model can adequately capture pharmacokinetic variation between special subpopulations. Here, we conduct an external evaluation comparing the predictive performance of published general and specialized population pharmacokinetic models in pediatric oncology and pediatric cardiovascular intensive care unit (CVICU) patients in order to address this question, and guide model selection decisions for model-informed precision dosing of vancomycin in these subpopulations.</p><p><strong>Methods: </strong>The predictive error, bias, and accuracy of two general, six oncology-supporting, and three CVICU-supporting pharmacokinetic models were compared in two multi-site data sets of pediatric oncology (N = 371, 1392 drug levels, 20 sites) and pediatric CVICU (N = 219, 1136 drug levels, 11 sites) patients, respectively. The best performing model(s) in each subpopulation were refit to evaluate whether predictive performance could be further improved over the published models.</p><p><strong>Results: </strong>We find that although specialized models performed better than general population models for pediatric CVICU patients, a general model (Colin 2019) performed better than all specialized models for pediatric oncology patients. We additionally report a refit version of the Shimamoto 2024 model for pediatric CVICU patients, which performed better than all published CVICU-supporting models in our data set.</p><p><strong>Conclusion: </strong>Population pharmacokinetic models developed on distinct pediatric subpopulations are not necessarily more fit-for-purpose than models developed on a general population. Both well-specified general models and specialized models may be capable of achieving suitable clinical performance in these subpopulations, and this assessment of model fit-for-purpose must be made on a case-by-case basis.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"527-543"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single Saliva Sample Model-Informed Precision Dosing of Levofloxacin for Multidrug-Resistant Tuberculosis.","authors":"Thi A Nguyen, Tri P Nguyen, Anh T Nguyen, Luong V Dinh, Hoa B Nguyen, Hoa D Vu, Tram N B Nguyen, Dang Vu, Greg J Fox, Jan-Willem C Alffenaar, Sophie L Stocker","doi":"10.1007/s40262-026-01619-3","DOIUrl":"10.1007/s40262-026-01619-3","url":null,"abstract":"<p><strong>Background and objectives: </strong>Levofloxacin is an essential drug in multidrug-resistant tuberculosis (MDR-TB) treatment, but high pharmacokinetic variability necessitates therapeutic drug monitoring (TDM) to optimise exposure and improve outcomes. Traditional TDM requires invasive blood sampling, limiting feasibility. Saliva sampling, a non-invasive matrix may simplify implementation. We aimed to develop a levofloxacin population pharmacokinetic (popPK) model integrating plasma and saliva data, and to evaluate saliva-based limited sampling strategies to support model-informed TDM for levofloxacin in practice.</p><p><strong>Methods: </strong>Adults receiving oral levofloxacin for ≥ 7 days had plasma and saliva samples collected at 0, 2, and 5 h post-dose. A plasma-and-saliva popPK model was developed using NONMEM, including covariate evaluation. Predictive performance of saliva-based limited sampling strategies for estimating plasma AUC₂₄ was assessed using Bayesian estimation and Monte Carlo simulations.</p><p><strong>Results: </strong>A total of 57 patients with 342 paired plasma-saliva samples were evaluated. One-compartment model incorporating saliva bio-compartment with first-order absorption (with a lag time) and elimination best described the data. No significant covariates were identified. Simulations showed that the three-point saliva strategy (0, 2, 5 h) predicted plasma AUC₂₄ within clinically acceptable limit (< 15% prediction error). A single 2-h sample yielded comparable accuracy. Two- and three-sample saliva strategies up to 16 h post-dose also showed clinically acceptable accuracy.</p><p><strong>Conclusions: </strong>The developed popPK model enables reliable estimation of levofloxacin exposure from limited saliva samples. A single 2-h post-dose saliva concentration may support model-informed levofloxacin TDM in routine MDR-TB care. This approach may be beneficial in settings where plasma-based TDM is logistically or ethically challenging.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"583-594"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodologies for Population Pharmacokinetic Modeling of Target-Site Drug Exposure: A Narrative Review of Current Strategies.","authors":"Michelle Mehciz, Pascale C S Rietveld, Birgit C P Koch, Tim Preijers","doi":"10.1007/s40262-026-01620-w","DOIUrl":"10.1007/s40262-026-01620-w","url":null,"abstract":"<p><p>Model-informed precision dosing (MIPD) is increasingly used to guide drug dosing based on population pharmacokinetic (popPK) models developed mainly using plasma concentration data. However, plasma levels may not always correlate well with drug concentrations at the site of action, potentially leading to under- or overestimation of target-site exposure. It is, therefore, important to evaluate which popPK modeling approaches effectively describe drug concentrations at target sites other than plasma to support the selection and implementation of appropriate modeling techniques. This review outlines four general modeling strategies described in literature characterizing the relationship between plasma and target-site drug concentrations. The first approach includes rate constants describing inflow and outflow, which is especially useful for unidirectional transport or large flow rate differences. Second, intercompartmental clearance models capture bidirectional transport with a single parameter that is directly comparable with elimination clearance or blood flow. Third, effect compartment models are used to describe delayed tissue distribution. Lastly, the target site can be modeled as part of either the central or the peripheral compartment. Although therapeutic drug monitoring (TDM) based on target-site concentrations has been suggested, implementation is limited by invasive sampling procedures, limited sample volumes, and the lack of established pharmacokinetic/pharmacodynamic targets. Nevertheless, even small differences in target-site exposure can result in clinical implications, and the applicability of drug monitoring using target-site concentrations has been shown in critically ill patients. In conclusion, target-site concentrations have been successfully predicted using different modeling methodologies and have demonstrated potential to optimize therapy in select clinical cases.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"497-513"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic-Pharmacodynamic Modeling and Simulation of Merigolix, a Nonpeptide Gonadotropin-Releasing Hormone Antagonist.","authors":"Soo Hyeon Bae, Jueun Kang, Sangil Jeon, Seon Mi Kim, Hun-Teak Kim, Seunghoon Han, Sungpil Han","doi":"10.1007/s40262-025-01595-0","DOIUrl":"10.1007/s40262-025-01595-0","url":null,"abstract":"<p><p>Gonadotropin-releasing hormone (GnRH) antagonists inhibit estrogen synthesis and secretion, making them promising treatment options for estrogen-dependent diseases, such as endometriosis. This study developed a population pharmacokinetic/pharmacodynamic (PK/PD) model for merigolix, a novel oral GnRH antagonist, to determine its optimal dosing in the treatment of endometriosis. Population PK/PD modeling was performed using NONMEM 7.4, incorporating data from phase I clinical studies involving single and multiple ascending dose (SAD and MAD) trials in healthy premenopausal volunteers. The PK profile was characterized using a two-compartment model incorporating first-order absorption and elimination processes. The temporal delay between merigolix concentration and subsequent estradiol (E2) suppression was described using an indirect response turnover model. The models were evaluated via visual predictive checks, goodness-of-fit plots, and bootstrap analysis. The PK model described merigolix concentrations across various doses (estimated clearance: 549 L/h, central volume of distribution: 1690 L). The PD model demonstrated dose-dependent E2 suppression (estimated maximum inhibitory effect [I_max]: 1, half-maximal inhibitory concentration [IC₅₀]: 0.209 ng/mL). Simulations suggested that, assuming a baseline E2 concentration of 100 pg/mL, daily doses of 120 and 160 mg achieved the clinically meaningful target E2 range of 20-40 pg/mL (partial suppression), while higher doses of 240 and 320 mg resulted in target E2 levels below 20 pg/mL (full suppression), effectively controlling symptoms and minimizing the risk of bone mineral density loss. This PK/PD model provides a quantitative framework for optimizing merigolix dosing and supports the selection of dosing regimens for future clinical trials, potentially offering a novel therapeutic option for endometriosis treatment.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"377-393"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of a Cystatin C-Based GFR Equation in a Population Pharmacokinetic Model of Methotrexate Clearance in Adult Patients with Lymphoma.","authors":"Zachary L Taylor, Erin F Barreto, Kristin C Cole, Andrew D Rule, Kianoush B Kashani, Nelson Leung, Carrie A Thompson, Thomas E Witzig, Laura B Ramsey, Jason N Barreto","doi":"10.1007/s40262-026-01618-4","DOIUrl":"10.1007/s40262-026-01618-4","url":null,"abstract":"<p><strong>Background: </strong>High-dose methotrexate (HDMTX) is a key treatment for lymphoma with central nervous system involvement. Whether incorporating cystatin C into glomerular filtration rate estimation improves methotrexate (MTX) clearance prediction remains unclear.</p><p><strong>Objectives: </strong>We aimed to evaluate whether cystatin C-inclusive glomerular filtration rate equations improve MTX clearance prediction and to explore the relationship between MTX exposure and acute kidney injury (AKI) in adult patients with lymphoma receiving HDMTX.</p><p><strong>Methods: </strong>This was a prospective single-center study performed on 80 adult patients with lymphoma receiving HDMTX (1.5-8 g/m²) over a 4-h infusion. A population pharmacokinetic model was constructed using data from 80 administrations of HDMTX and 427 serum MTX concentrations. The population pharmacokinetic model estimated MTX concentrations were included in a logistic regression to assess the relationship between MTX exposure and AKI.</p><p><strong>Results: </strong>A two-compartment model best described the pharmacokinetic data, with baseline albumin and CKD-EPI creatinine-cystatin C (eGFRCr-CysC) as significant covariates on clearance. Seventeen patients (21%) developed any-stage AKI. Among those receiving ≤ 3.5 g/m², model-estimated 4-h MTX concentrations were associated with AKI (odds ratio: 1.02 per µmol/L; p = 0.0038), with an optimal threshold of 160 µmol/L (area under the concentration-time curve: 0.818). Patients above this threshold were 22 times more likely to experience AKI (p = 0.0005). This association was not observed in patients treated with 8 g/m². Despite a lower dose and exposure, patients receiving ≤ 3.5 g/m² demonstrated a stronger concentration-toxicity relationship.</p><p><strong>Conclusions: </strong>Our results support the use of cystatin C-inclusive glomerular filtration rate estimates in MTX pharmacokinetic modeling and suggest early MTX concentration sampling may identify AKI risk, enabling proactive, AKI-mitigating clinical interventions during HDMTX therapy.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":"65 3","pages":"465-477"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12960310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Pharmacokinetic Analysis of Intravenous Fluconazole in Adult Patients Undergoing Mechanical Circulatory Support Device Implantation.","authors":"Kelly A Cairns, Maria Patricia Hernandez-Mitre, Trisha N Peel, Iain J Abbott, David M Kaye, Silvana Marasco, David Daly, Victoria Warner, Anna Coldham, Jeffrey D Pope, Hans G Schneider, Michael J Dooley, Xin Liu, Jason A Roberts, Andrew A Udy","doi":"10.1007/s40262-025-01607-z","DOIUrl":"10.1007/s40262-025-01607-z","url":null,"abstract":"<p><strong>Background and objective: </strong>There is limited information on the pharmacokinetics and optimal dosing of fluconazole in patients undergoing mechanical circulatory support (MCS) device implantation.</p><p><strong>Aim: </strong>The aim of this study was to describe fluconazole pharmacokinetics and identify dosing regimens that achieve pharmacokinetic/pharmacodynamic targets in this patient cohort.</p><p><strong>Methods: </strong>In this prospective, single-centre study, adults undergoing MCS device implantation received intravenous fluconazole 200 mg or 400 mg, continued once daily for 5 days. Fluconazole concentrations were measured at four peri-operative time points, on return to the intensive care unit, and on days 3 and 5 following implantation. The area under the concentration-time curve from time zero to 24 h (AUC_0-24) was estimated, with target exposures defined as AUC_0-24/minimum inhibitory concentration (MIC) ≥ 50 for prophylaxis and AUC_0-24/MIC ≥ 100 for therapy. Population pharmacokinetic modelling was performed using non-linear mixed-effects methods and for Monte Carlo dosing simulations.</p><p><strong>Results: </strong>Sixty-five fluconazole concentrations from 10 male patients (median age 51.5 years; IQR 50.0-57.0) were included. A two-compartment model including an additional renal replacement therapy (RRT)-dependent clearance pathway best described the data. Parameter estimates from the final model included a central volume of distribution of 5.75 L, non-RRT clearance of 0.45 L/h, and RRT clearance of 2.22 L/h. Simulations showed that doses of 800 mg or 12 mg/kg would be required for the highest probability of target attainment for Candida fluconazole MICs up to 4 mg/L (AUC_0-24/MIC ≥ 50) and 2 mg/L (AUC_0-24/MIC ≥ 100).</p><p><strong>Conclusion: </strong>In patients undergoing MCS device implantation, intravenous fluconazole 200 mg administered pre-operatively and continued daily for 5 days is insufficient for Candida spp. with MICs > 1 mg/L (prophylaxis, AUC_0-24/MIC ≥ 50) and > 0.5 mg/L (treatment, AUC_0-24/MIC ≥ 100).</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"395-404"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Pharmacokinetics of Intravenous Cefuroxime in Plasma and Bone of Patients with Prosthetic Joint Infection: Is There Room for Dose Optimization?","authors":"Gerbert Coen de Waard, Qiaolin Zhao, Ewout S Veltman, Jakob van Oldenrijk, P Koen Bos, Soma Bahmany, Anouk Muller, Tim Preijers, Birgit C P Koch","doi":"10.1007/s40262-025-01597-y","DOIUrl":"10.1007/s40262-025-01597-y","url":null,"abstract":"<p><strong>Background and objective: </strong>Prosthetic joint infections are serious infections that require perioperative antibiotic prophylaxis. Cefuroxime may be used as prophylaxis, and this study aims to evaluate the current dosing regimen to prevent infection during the perioperative period by performing population pharmacokinetic (PK) analysis of plasma and bone in patients with prosthetic joint infection (PJI).</p><p><strong>Methods: </strong>Both plasma and bone samples were taken perioperatively and analyzed using NONMEM. Monte Carlo simulations were performed to determine the probability of target attainment (PTA) in both plasma and bone of various dosing regimens.</p><p><strong>Results: </strong>A total of 44 plasma and 38 bone samples from 25 patients were included. The median bone concentration at 30-60 min after administration was 18.2 (9.9-25.3) mg/L and the bone-to-plasma ratio was 0.269 (interquartile range [IQR] 0.179-0.269), while the median bone concentration at 90-120 min after administration was 12.6 (5.9-18.6) mg/L and the bone-to-plasma ratio was 0.125 (IQR 0.073-0.160). A two-compartment model with allometric scaling and proportional errors best described plasma and bone concentrations. Only estimated glomerular filtration rate could partly explain the inter-individual variability (IIV) of clearance (CL). A single dose of 1500 mg cefuroxime failed to maintain bone concentrations above target concentrations for Staphylococcus aureus beyond 3.83 h post administration.</p><p><strong>Conclusion: </strong>A population PK model was developed to characterize the disposition of cefuroxime in both plasma and bone compartments. Although adequate cefuroxime bone penetration within 1 h was observed in patients with PJI with rapid clearance, simulations predicted less optimal levels of cefuroxime after 3.5 h. The clinical implications need to be researched and confirmed.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"405-415"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}