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Is there potential for therapeutic drug monitoring of biologic agents in rheumatoid arthritis?

Carla Bastida, Virginia Ruíz, Mariona Pascal, Jordi Yagüe, Raimon Sanmartí, Dolors Soy
2017 British Journal of Clinical Pharmacology  
The literature relating to their concentration-effect relationship and the use of pharmacokinetic-pharmacodynamic modelling to optimize drug regimens is analysed.  ...  The use of biologics has significantly changed the management of rheumatoid arthritis over the last decade, becoming the cornerstone treatment for many patients.  ...  [62] conducted a modelling and simulation study in RA patients treated with abatacept.  ... 
doi:10.1111/bcp.13192 pmid:27990682 pmcid:PMC5401978 fatcat:hnonsfcwlfetje3zf52u5ormye

Modelling c-Abl Signalling in Activated Neutrophils: the Anti-inflammatory Effect of Seliciclib

Robert Jackson, Tomas Radivoyevitch
2013 BioDiscovery  
We present here a model of neutrophil kinetics that simulates the principal pathways of c-Abl signalling and use it to explore possible treatment options for inflammatory lung disease.  ...  The normally short-lived tissue neutrophils are then unable to enter apoptosis. c-Abl also causes release of reactive oxygen species (ROS) from the mitochondria of the activated neutrophils.  ...  It is under clinical evaluation for treatment of rheumatoid arthritis, a disease where tissue damage is caused by invasion of activated neutrophils. Simulation 5 modelled the effect of 10 nM MOR103.  ... 
doi:10.7750/biodiscovery.2013.7.4 pmid:24765523 pmcid:PMC3994723 fatcat:ninnythmn5afzgbhhnzfruajo4

Sustained release ophthalmic dexamethasone: In vitro in vivo correlations derived from the PK-Eye

Sahar Awwad, Richard M. Day, Peng T. Khaw, Steve Brocchini, Hala M. Fadda
2017 International Journal of Pharmaceutics  
The dexamethasone loaded microparticles were evaluated using a two-compartment, in vitro aqueous outflow model of the eye (PK-Eye) that estimates drug clearance time from the back of the eye via aqueous  ...  The prediction of human clearance times of permeable molecules from the vitreous compartment can be determined by accounting for drug permeation and determining the experimental clearance via the anterior  ...  microparticles containing particulate infliximab was 60.4 ± 5.9% compared with 37.9 ± 14.4% for microspheres containing an emulsion of infliximab. 21 Degradable polymeric microparticles can enable a  ... 
doi:10.1016/j.ijpharm.2017.02.047 pmid:28232270 fatcat:7gupod6kzjgm7ellf5334e5hwm

An immune therapy model for effective treatment on inflammatory bowel disease

Anna Park, Sangil Kim, Il Hyo Jung, Jong Hyuk Byun, Pinyi Lu
2020 PLoS ONE  
For this, we defined the interval of healthy individual, and examined the frequency of compartments such as T cells and cytokines considered in the model maintain the normal state.  ...  In this work, we proposed an immune therapy model for effective treatment strategy through mathematical modeling for patients with IBD.  ...  Our model is substituted with an additional compartment for drug intervention.  ... 
doi:10.1371/journal.pone.0238918 pmid:32970698 fatcat:fe62y6izxvadjoghwyhzbqkyuu

Promising Role of Toll-Like Receptor 8 Agonist in Concert with Prostratin for Activation of Silent HIV

M. A. Rochat, E. Schlaepfer, R. F. Speck, Frank Kirchhoff
2016 Journal of Virology  
The persistence of latently HIV-infected cells in patients under combined antiretroviral treatment (cART) remains the major hurdle for HIV eradication.  ...  Moreover, TLR8 triggering may reverse exhaustion of HIV-specific cytotoxic T lymphocytes that might be essential for killing or constraining the latently infected cells.  ...  ACKNOWLEDGMENTS We thank the patients for kindly participating in this study.  ... 
doi:10.1128/jvi.02084-16 pmid:27928016 pmcid:PMC5286885 fatcat:loq6vylunngivhaodiowrlw2xm

Clinical Pharmacokinetics and Pharmacodynamics of Biologic Therapeutics for Treatment of Systemic Lupus Erythematosus

Tian Yu, Elena Y. Enioutina, Hermine I. Brunner, Alexander A. Vinks, Catherine M. Sherwin
2016 Clinical Pharmacokinetics  
The development of linked pharmacokinetic-pharmacodynamic models incorporating SLE disease biomarkers are an attractive strategy for use in dosing regimen simulation and optimization.  ...  The population pharmacokinetics of monoclonal antibodies were best described by a two-compartment model with central clearance and steady-state volume of distribution ranging from 0.176 to 0.215 L/day  ...  of the minimal lumped models to classical compartment models.  ... 
doi:10.1007/s40262-016-0426-z pmid:27384528 pmcid:PMC5575762 fatcat:eyruxqgwq5dt5gi24bulbjweuu

Opportunistic autoimmune disorders

Yi-chi M. Kong, Wei-Zen Wei, Yaron Tomer
2010 Annals of the New York Academy of Sciences  
Rapid advances in our understanding of the immune network have led to treatment modalities for malignancies and autoimmune diseases based on modulation of the immune response.  ...  Our combination models to study the balance between thyroid autoimmunity and tumor immunity upon regulatory T-cell perturbation are briefly described.  ...  Acknowledgments This work was supported by the National Institutes of Health DK45960 (to Y.K.), CA125680 (to W.W.), and DK61659, DK073681, and a VA Merit Award (to Y.T.).  ... 
doi:10.1111/j.1749-6632.2009.05138.x pmid:20146718 pmcid:PMC3815555 fatcat:drkqxybk25bkthd6tllymcm2me

Alternate virtual populations elucidate the type I interferon signature predictive of the response to rituximab in rheumatoid arthritis

Brian J Schmidt, Fergal P Casey, Thomas Paterson, Jason R Chan
2013 BMC Bioinformatics  
However, there is a lack of tools to simultaneously (1) calibrate the prevalence of mechanistically distinct, large sets of virtual patients so their simulated responses statistically match phenotypic  ...  MAPEL is the first algorithm for developing weighted virtual populations based on biosimulation results that enables the rapid development of an ensemble of alternate virtual population hypotheses, each  ...  We present the results for the adjusted R 2 for linear models constructed for each VPop as a function of model size in Additional file 3.  ... 
doi:10.1186/1471-2105-14-221 pmid:23841912 pmcid:PMC3717130 fatcat:epzof2qwonc35hi5efmrpjc5ue

Clinical Pharmacology of Alemtuzumab, an Anti-CD52 Immunomodulator, in Multiple Sclerosis

Zhaoyang Li, Susan Richards, Howard K. Surks, Alan Jacobs, Michael A. Panzara
2018 Clinical and Experimental Immunology  
In the Phase II/III trials, patients received 12 or 24 mg/day of alemtuzumab in two treatment courses (5 days for course 1 and 3 days for course 2), 12 months apart.  ...  Alemtuzumab rapidly depleted circulating T and B lymphocytes, with the lowest observed values occurring within days.  ...  We thank the Sanofi Clinical, Biostatistics and Bioanalytical teams for their contributions to the completion of these studies. ClinicalTrials.gov Identifiers Author contributions Z. L., S.  ... 
doi:10.1111/cei.13208 pmid:30144037 pmcid:PMC6231011 fatcat:ne64b73qcvfphk3tiyjqkihaki

Role of CXCL13 in the formation of the meningeal tertiary lymphoid organ in multiple sclerosis

Ana C. Londoño, Carlos A. Mora
2018 F1000Research  
Immunomodulatory therapies available for the treatment of patients with multiple sclerosis (MS) accomplish control and neutralization of peripheral immune cells involved in the activity of the disease  ...  In animal models of experimental autoimmune encephalomyelitis (EAE), the presence of CXCL13 has been associated with disease activity and the blockade of this chemokine could work as a potential complementary  ...  of B cell depleting therapy 22,33,45 .  ... 
doi:10.12688/f1000research.14556.3 fatcat:rnp7li3ix5f3bbi3oio2m2qxye

Role of CXCL13 in the formation of the meningeal tertiary lymphoid organ in multiple sclerosis

Ana C. Londoño, Carlos A. Mora
2018 F1000Research  
Immunomodulatory therapies available for the treatment of patients with multiple sclerosis (MS) accomplish control and neutralization of peripheral immune cells involved in the activity of the disease  ...  In animal models of experimental autoimmune encephalomyelitis, a blockage of CXCL13 has resulted in modification of the disease course and it could work as a potential complementary therapeutic strategy  ...  Financial support for the on-line publication of this article was provided by The Department of Neurology, MedStar Georgetown University Hospital.  ... 
doi:10.12688/f1000research.14556.1 pmid:30345018 pmcid:PMC6171727 fatcat:qt6gmtxdyvdbjle6zkf2olf4eu

Modeling Pharmacokinetics and Pharmacodynamics of Therapeutic Antibodies: Progress, Challenges, and Future Directions

Yu Tang, Yanguang Cao
2021 Pharmaceutics  
This review summarized the progress, challenges, and future directions in modeling antibody PK/PD and highlighted the potential of applying mechanistic models addressing the development questions.  ...  novel antibody formats, and high rates of treatment resistance.  ...  Conflicts of Interest: There is no conflict of interest.  ... 
doi:10.3390/pharmaceutics13030422 pmid:33800976 fatcat:io4kzyakrzbnzcv7xgqd6v442y

Update on Chronic Rejection After Intestinal Transplant: An Overview From Experimental Settings to Clinical Outcomes

Augusto Lauro, Ignazio R. Marino
2019 Experimental and Clinical Transplantation  
Chronic rejection affects the long-term survival of solid-organ transplants, accounting for an incidence of between 5% and 10% after intestinal/multivisceral transplant.  ...  Extensive research, through animal models, has been performed over the past 20 years to clarify the complex immune-and nonimmune-mediated mechanisms behind the development of chronic allograft enteropathy  ...  bone marrow compartment.  ... 
doi:10.6002/ect.mesot2018.l32 fatcat:fwe2biokcrg3zpb4toz7rsyfny

Biologics During Pregnancy and Breastfeeding Among Women With Rheumatic Diseases: Safety Clinical Evidence on the Road

Asmaa Beltagy, Azin Aghamajidi, Laura Trespidi, Wally Ossola, Pier Luigi Meroni
2021 Frontiers in Pharmacology  
Data on breastfeeding are currently available for several biologics.  ...  Subsequent observations are suggesting a comparable safety for the soluble TNFα receptor etanercept.  ...  T-and B-regulatory compartment, increased eosinophil counts in cord blood Esteve-Solé et al. (2017) Abnormal infant's' immune response to BCG vaccine in one case of infliximab exposure Cheent et  ... 
doi:10.3389/fphar.2021.621247 pmid:34122062 pmcid:PMC8189556 fatcat:d6yrwmdonrbvtbzhdo2xp3naji

Pharmacokinetic/Pharmacodynamic Modeling in Inflammation

Hoi-Kei Lon, Dongyang Liu, William J. Jusko
2012 Critical reviews in biomedical engineering  
This review illustrates the state of the art in modeling the effects of diverse drugs for treating inflammation, describes relevant biomarkers amenable to modeling, and summarizes major advantages and  ...  More advanced mechanistic models should allow evaluation of the roles of some key mediators in disease progression, assess drug interactions, and better translate drug properties from in vitro and animal  ...  GM 24211 from the National Institutes of Health and fellowship support from Amgen Pharmaceuticals (HKL) and Hoffman LaRoche (DL).  ... 
doi:10.1615/critrevbiomedeng.v40.i4.50 pmid:23140121 pmcid:PMC3538354 fatcat:cxyg6uux75cmrfuyt532hczuq4
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