Journal of Pharmacokinetics and Pharmacodynamics最新文献

{"title":"QSP model for AAV-mediated antibody delivery in rat brain.","authors":"Shufang Liu, Ekram Ahmed Chowdhury, Shengjia Wu, Guy Meno-Tetang, Dhaval K Shah","doi":"10.1007/s10928-026-10051-w","DOIUrl":"10.1007/s10928-026-10051-w","url":null,"abstract":"<p><p>Adeno-associated virus (AAV) mediated monoclonal antibody (mAb) expression in the brain represents an exciting one-and-done therapeutic option for many central nervous system (CNS) disorders that are hard to treat following systemic mAb administration. To facilitate the development of such AAV therapies, here we have developed an AAV-transgene-target quantitative systems pharmacology (QSP) model that can simultaneously characterize the disposition of AAV, expressed antibody, therapeutic target, and the mAb-target complex in plasma, tissues, and the brain. The model was built by integrating previously published platform physiologically based pharmacokinetic (PBPK) models for AAV, protein therapeutics, and brain, with special emphasis on transport pathways and transduction mechanisms within the brain. The developed QSP model was able to capture the pharmacokinetics of AAV and the expressed mAb in the systemic circulation and brain tissues following AAV administration via diverse routes in the rats. The model suggested that intra-cisternal magna injection of medium AAV dose or intrastriatal injection of low AAV dose would provide better therapeutic options compared to intravenous administration of high AAV dose. Locally administered AAV was predicted to lead to sufficient antibody exposure and substantial target engagement in cerebrospinal fluid (CSF) and interstitial fluid (ISF), while minimizing systemic AAV and antibody exposure, leading to maximal efficacy and minimal toxicity. Overall, the present work not only supports cross-species and cross-serotypes translational potential of previously published AAV PBPK model, but also highlights application of QSP modeling to guide the development of AAV therapies for neurological disorders.</p>","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":"53 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential expression of monoclonal antibody in rat brain following systemic and local administration of AAV.","authors":"Ekram Ahmed Chowdhury, Guy Meno-Tetang, Shufang Liu, Shengjia Wu, Navya Desireddy, Anthony Jerez, Leeha Mahmood, Aneesh Rajwade, Sidhaarth Bulusu, Tanguy Jamier, Annalisa Nucitelli, Fiona Cusdin, Claire Dobson, Dhaval K Shah","doi":"10.1007/s10928-026-10050-x","DOIUrl":"10.1007/s10928-026-10050-x","url":null,"abstract":"<p><p>Adeno-associated virus (AAV) mediated monoclonal antibody (mAb) expression in the central nervous system (CNS) constitutes a promising approach for treating various CNS disorders. However, a comprehensive understanding of AAV biodistribution and antibody expression in the brain following viral vector administration via different local CNS routes and systemic administration is not well established. AAV9 and AAV5 vectors encoding antibody against a protein associated with neurodegeneration (i.e., anti-Target-X mAb), as well as AAV9 encoding a control antibody (Ctrl-mAb), were administered to rats via intravenous (IV), intra-cisterna magna (ICM), and intrastriatal (IST) routes. Effect of immunosuppression regimen was also investigated. Blood/plasma concentrations of the vector and mAb were measured at day 21 and day 56, the latter only for ICM group. AAV and mAb concentrations in different brain regions, interstitial fluid (ISF), cerebrospinal fluid (CSF), and some peripheral tissues were analyzed. Both the IST and ICM routes showed dose-proportional, and higher vector biodistribution and mAb expression in the brain compared to the IV route. Twenty-fold lower AAV dose administered via IST route produced similar transgene expression higher dose administered via ICM route. Non-immunosuppressed rats exhibited a sharp decline in mAb plasma concentration after 2nd week and lower brain and tissue homogenate concentrations at 3-week. IST and ICM administration of AAV results in higher and more sustained expression of antibody in the brain compared to IV delivery, particularly when immune responses are controlled using concomitant immunosuppression regimen.</p>","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":"53 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13372995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A simple algebraic expression can determine if a drug's clearance is non-specific or target-mediated.","authors":"Liam V Brown, Alberto Ippolito, Mark Penney, Rhys DO Jones","doi":"10.1007/s10928-026-10043-w","DOIUrl":"10.1007/s10928-026-10043-w","url":null,"abstract":"<p><p>Target-mediated drug distribution (TMDD) is typically classified by accelerated removal of drug after serum concentration drops below a critical level. Susceptible drugs would be dosed to a schedule that maintains exposure above this level, where concentration drops monoexponentially. Out-dosing TMDD often implies that target binding is saturated or degraded. T-cell engagers and other biologics are often given with low dosages which make out-dosing TMDD unrealistic, yet are also typically observed to have monoexponential elimination. It can be challenging to determine whether such a concentration-time relationship is due to TMDD or standard non-specific (intrinsic) routes of clearance, and more so to scale this clearance from preclinical settings, as TMDD-driven clearance may not scale allometrically like intrinsic clearance. In this work, we derived an algebraic expression for the proportion of clearance that is target-mediated or intrinsic, which requires only the intrinsic half-life and the target receptor's concentration, turnover rate and binding affinity for the drug. We further show that the typical transition from monoexponential decline of serum concentrations to accelerated, target-driven clearance occurs at concentrations given by two expressions in those same parameters. We apply the equations to published data for monoclonal antibodies and T-cell engagers, finding that we consistently characterize their clearance as expected. These expressions can be used to determine if a drug's clearance would be expected to be driven by target-mediated or non-specific routes at pharmacologically active concentrations, and hence how to accurately translate pharmacokinetic properties from preclinical species to human, a process that is essential for drug development.</p>","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":"53 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13372877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Longitudinal Disease Progression Model Characterizing Endoscopic Response and Remission in Crohn's Disease.","authors":"Anita Moein, Jurgen Langenhorst, Nastya Kassir","doi":"10.1007/s10928-026-10042-x","DOIUrl":"10.1007/s10928-026-10042-x","url":null,"abstract":"<p><p>Crohn's disease (CD) is a heterogeneous, progressive inflammatory bowel disease in which substantial placebo effects often confound assessment of therapeutic efficacy. A placebo-based disease model was developed using Simple Endoscopic Score for Crohn's Disease (SES-CD) within an item-level response theory-bounded integer (IRT-BI) and full random effects models (FREM) framework. Longitudinal SES-CD data from 155 placebo-treated patients in the Phase 3 BERGAMOT-trial were analyzed. Each SES-CD subscore, across five intestinal segments, was described by a bounded-integer model and linked through a latent disease variable capturing a mono-exponential placebo trajectory. Endoscopic response (≥50% reduction from baseline SES-CD) and remission (SES-CD 0-2) were defined according to the FDA guidance. IRT-BI model adequately characterized longitudinal trajectories of all SES-CD subscores and accurately predicted individual patient endoscopic response and remission, with predictive accuracy exceeding 89% for responders and 85% for non-responders. Visual predictive checks showed that observed mean trajectories for all 20 SES-CD subscores were within the 90% confidence intervals across the 66-week trial. Population maximum placebo response (R_MaxPL) was estimated at -0.220 with a time to half-maximal effect of 13.8 weeks. Covariate analysis identified elevated baseline C-reactive protein and fecal calprotectin correlated to reduced R_MaxPL, whereas TNF-naïve status was associated with increased R_MaxPL. This is first application of an integrated item-level IRT-BI-FREM approach in CD, enabling robust characterization of placebo response and identification of clinically relevant covariates. By providing quantitative framework for isolating drug-effects from placebo-response, this model aligns with FDA model-informed drug development priorities and supports efficient, targeted, and informative clinical trials.Clinical Trial RegistrationNCT02394028 Registered March 20, 2015.</p>","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":"53 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13356052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148421740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The evolution of nonlinear mixed effects modeling in pharmacometrics: toward AI-based variational autoencoders.","authors":"Jan Rohleff, Gilbert Koch, Johannes Schropp","doi":"10.1007/s10928-026-10044-9","DOIUrl":"10.1007/s10928-026-10044-9","url":null,"abstract":"<p><p>The evolution of nonlinear mixed effects (NLME) modeling reflects a continuous cycle of innovation based on advances in numerical methods and computational power. This commentary outlines the evolution of NLME modeling that began with linearization-based approaches in the 1980s, progressed through sampling-based methods in the 2000s, and is now entering a new phase shaped by AI. Variational autoencoders bridge classical NLME modeling with AI-based methods allowing the development and application of AI-augmented PMX models. This opens the route for integrating multimodal data and addressing increasingly complex modeling challenges.</p>","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":"53 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13346202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148411813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing quantitative clinical pharmacology competencies in Francophone Africa through an on-line learning framework.","authors":"Nour Chtiba, Sihem Ait-Oudhia, Sonia Khier, Anna Chan Kwong, Innocent G Asiimwe, Florence Gattacceca, Miriam Razgallah Khrouf, Paul Baverel, Celine Sarr, Anaïs Glatard, Julie Bertrand, Nada Abla, Maddlie Bardol, Salim Bouchene, Marylore Chenel, Emmanuelle Comets, Paolo Denti, Alexandre Duong, Mor Fall, Fanny Gallais, Kamunkwala Gausi, Khalil Ben Hassine, Amelie Marsot, Sophie Peigné, Elodie L Plan, Myrtille Vivien, Jean-Louis Steimer, Leon Aarons, Goonaseelan Colin Pillai","doi":"10.1007/s10928-026-10046-7","DOIUrl":"10.1007/s10928-026-10046-7","url":null,"abstract":"<p><p>Clinical pharmacology and pharmacometrics are central to understanding patient response to new and existing therapies, yet access to training in Africa remains limited, particularly in francophone countries where language is a barrier. We report the design and implementation of a 12-week French-language online course combining asynchronous lessons with live interactive sessions. The inaugural cohort enrolled 72 students from Senegal (n = 37), Tunisia (n = 24), and the Democratic Republic of the Congo (n = 11). While only one-third completed the full program, all survey respondents judged the course useful, highlighting clear objectives and adequate preparation time. Challenges related to perceived workload, time-zone difference in scheduling, and internet connectivity were reported by participants. A second iteration of the course hosted by the Tunisia Chapter of Pharmacometrics Africa has just completed and will gather further feedback and attempt to address lessons learnt. This proof-of-concept hands-on educational program demonstrates that delivering training in French through an online format can effectively expand access to pharmacometrics education in Africa. Strengthening local institutional partnerships to take on technical support will be critical to improving participant retention and ensuring program sustainability. Moreover, this model could be adapted to other languages and extended to additional regions, thereby promoting more inclusive global capacity building.</p>","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":"53 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging the operational gap in population pharmacokinetic-pharmacodynamic analysis: an international perspective on the 2025 Chinese group standard.","authors":"Zheng Jiao, Jun-Jie Ding, Guang-Li Ma, Xuan Zhou, Lu-Jin Li, Kun Wang, Liang Li, Yu-Peng Ren","doi":"10.1007/s10928-026-10045-8","DOIUrl":"10.1007/s10928-026-10045-8","url":null,"abstract":"<p><p>Population pharmacokinetic/pharmacodynamic (PPK/PD) modeling is a key component of model-informed drug development and model-informed precision dosing. Regulatory agencies in the United States, Europe, Japan, and China, together with the recently adopted ICH M15 guideline, have established high-level principles for the conduct, evaluation, and reporting of population modeling analyses. However, many practical implementation details are intentionally left to sponsors, investigators, and analysts. Although this flexibility accommodates diverse objectives, data structures, therapeutic areas, and decision contexts, it may also contribute to inter-analyst variability and limit the reproducibility, transparency, and consistency of PPK/PD practice. This review discusses the 2025 Chinese Pharmacological Society group standard for PPK/PD analysis from an international and implementation-oriented perspective. The standard describes a stepwise analytical lifecycle comprising pre-analysis preparation, base model development, final model establishment, model application, and reporting, with model evaluation embedded iteratively throughout the process. It also formalizes operational elements often implicit or under-specified in existing guidance, including a prospective Population Modeling Analysis Plan, distinction between exploratory and confirmatory analyses, prioritization of decision-relevant parameters, staged verification checkpoints, a five-element risk-management cycle, and ethical considerations related to data governance and equitable model application. We position the Chinese group standard as an analyst-level operational reference that complements, rather than replaces or duplicates, the decision-level assessment framework provided by ICH M15. Although developed within the Chinese regulatory and professional context, the structured workflow described in the standard may provide a practical reference for organizations seeking to improve the reproducibility, transparency, and consistency of PPK/PD analyses internationally.</p>","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":"53 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cohort population analysis of sparse data: Dexamethasone pharmacokinetics in mother and fetus based on blood sampling at birth.","authors":"Wojciech Krzyzanski","doi":"10.1007/s10928-026-10048-5","DOIUrl":"10.1007/s10928-026-10048-5","url":null,"abstract":"<p><p>We introduced an estimation technique for mixed effect models that stems from non-parametric methods of estimation and fully parametric mixture models with cohort population as a central concept. The cohort population partitions data variability into between-cohorts and residual variabilities. This permits maximum likelihood estimates of model parameters from sparse data such as one observation per subject. Our second objective was to test robustness of cohort population estimation technique using previously published pharmacokinetic data on dexamethasone in parturient women. We performed two studies. In Study I we generated 100 dense and sparse datasets and refitted the data to quantify the difference between parameter estimates obtained by the cohort population model and the standard estimation methods. In Study II we evaluated robustness of cohort population model using dexamethasone maternal and fetal plasma concentrations obtained at childbirth after intramuscular injection of two 8 mg antenatal doses of dexamethasone phosphate in pregnant women. We implemented in NONMEM 7.6 the 3-cohort population as a mixture population model and applied first order conditional estimation, stochastic approximation, and importance sampling methods for parameter estimation. We showed that cohort estimation can quantify the variability in (log)normal populations where between-cohort variability is a substitute for between-subject variability. The cohort estimates of structural model parameters were equally accurate than the standard estimates and the accuracy and precision of estimates of inter-individual variability parameters for sparse data were better than for the standard maximum likelihood methods. Finally, we showed that the cohort population estimates provided meaningful quantification of one compartment model parameters for dexamethasone in parturient women where data were limited only to one blood sample per subject drawn after childbirth.</p>","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":"53 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing Subcutaneous Antibody Dosing Regimens Through Operating Space Maps: rHuPH20 Case Study.","authors":"Ryan P Nolan, Harish Chintakuntla","doi":"10.1007/s10928-026-10037-8","DOIUrl":"10.1007/s10928-026-10037-8","url":null,"abstract":"<p><p>Therapeutic antibody dosing regimens are often constrained by formulation and administration factors that limit flexibility in dose and schedule. Subcutaneous (SC) delivery offers advantages over intravenous (IV) administration-such as improved convenience and potentially more favorable pharmacokinetic (PK) profiles-but is typically restricted by injection volume, requiring lower doses and more frequent dosing. Recombinant human hyaluronidase PH20 (rHuPH20) enables rapid administration of high-dose, high-volume therapeutics, thereby expanding the feasible SC delivery landscape. Despite these advances, biopharmaceutical development teams often lack tools to quantify the strategic impact of SC-enabling technologies and interpret PK simulations in a decision-ready format. This work introduces Operating Space Maps, a visual PK simulation framework that organizes multiple dosing scenarios into an intuitive landscape of dose-frequency options. Using rHuPH20 as a case study, a two-compartment PK model is applied to simulate representative antibody regimens for two illustrative scenarios: converting IV regimens to SC with rHuPH20 and extending SC dosing intervals beyond standard limits with rHuPH20. For example, relative to a 1000 mg IV benchmark regimen, a 1400 mg SC dose with rHuPH20 maintains equivalent average exposure while reducing C_max by approximately 50%. The methodology is broadly applicable to other SC-enabling technologies for which sufficient foundational data exist to parameterize the model. By making trade-offs between C_min, C_avg, and C_max explicit and integrating SC delivery constraints, Operating Space Maps enable cross-functional development teams to evaluate regimen feasibility, optimize target product profiles, and guide strategic decisions early in development.</p>","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":"53 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13314913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148352335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic modeling of FcRn-dependent IgG drug interactions: Clinical applications and dosing implications.","authors":"Paridhi Gupta, Vivaswath S Ayyar","doi":"10.1007/s10928-026-10034-x","DOIUrl":"10.1007/s10928-026-10034-x","url":null,"abstract":"<p><p>Concomitant use of intravenous immunoglobulin (IVIG) with monoclonal antibodies (mAbs) or bispecific T-cell engagers (TCEs) is routinely encountered across autoimmune diseases, B-cell malignancies, immunodeficiencies, and transplantation. These therapies share a key salvage pathway through the neonatal Fc receptor (FcRn), raising the potential for pharmacokinetic (PK) and pharmacodynamic (PD) interactions. A mechanistic model of IgG disposition originally developed in mice was extended and revalidated with an array of human datasets to investigate how IVIG dose, timing, and IgG pool dynamics influence therapeutic IgG behavior and PK/PD outcomes. The model captures endogenous and exogenous IgG kinetics via FcRn-mediated recycling in a peripheral (endosomal) compartment, coupled with first-order catabolism of unbound IgG. Simultaneous model-fitting against clinical data reproduced serum IgG kinetics and endogenous/pathogenic IgG reductions across autoimmune and transplant settings. It recapitulated the ~36% decrease in tesidolumab exposure observed during IVIG co-administration in renal transplant recipients, largely explaining associated PD alterations. In pemphigus vulgaris, model-predicted total IgG increases following 2 g/kg IVIG aligned with observed values. Predicted endogenous IgG decline mirrored the time-course of anti-BP180 autoantibody reduction. Upon suitably adapting and requalifying the model, it was applied to examine two co-therapy scenarios: (i) IVIG supplementation in multiple myeloma patients receiving the TCE teclistamab, and (ii) immunosuppressive rituximab-IVIG co-therapy for transplant desensitization. Simulations revealed how IVIG co-therapy may alter mAb effects depending on IVIG regimen, IgG pool dynamics, and the exposure-response relationship of the mAb. This generalizable framework supports model-informed drug development and prospective management of therapeutic IgG interactions.</p>","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":"53 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148330554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}