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Biological therapy is very effective for treating patients with moderate to severe inflammatory bowel disease (IBD). However, up to 40% can have primary non-response, and up to 50% of the patients can experience a loss of response to anti-tumor necrosis factor therapy. These undesirable outcomes can be attributed to either a mechanistic failure or pharmacokinetic (PK) issues characterized by an inadequate drug exposure and a high drug clearance. There are several factors associated with accelerated clearance of biologics including increased body weight, low serum albumin and immunogenicity. Drug clearance has gained a lot of attention recently as cumulative data suggest that there is an association between drug clearance and therapeutic outcomes in patients with IBD. Moreover, clearance is used by model informed precision dosing (MIDP) tools, or PK dashboards, to adjust the dosing for reaching a target drug concentration threshold towards a more personalized application of TDM. However, the role of drug clearance in clinical practice is yet to be determined. This comprehensive review aims to present data regarding the variables affecting the clearance of specific biologics, the association of clearance with therapeutic outcomes and the role of clearance monitoring and MIPD in patients with IBD.
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http://dx.doi.org/10.3390/jcm12227132 | DOI Listing |
Biomacromolecules
September 2025
State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China.
Triple-negative breast cancer (TNBC) remains a formidable clinical challenge due to its aggressive behavior, lack of therapeutic targets, and poor prognosis. The PI3K/AKT/mTOR pathway is highly activated in TNBC, making it a promising therapeutic target. Conventional PEGylated nanocarriers often face challenges, such as accelerated blood clearance and lysosomal trapping.
View Article and Find Full Text PDFJ Antimicrob Chemother
September 2025
Department of Pharmaceutical Sciences, University of Michigan College of Pharmacy, Ann Arbor, MI 48109, USA.
Background: Synergy between antibiotic pairs is typically discovered using chequerboard assays that assume uniform, static drug exposure; however, such conditions rarely apply in vivo. Dynamic and heterogeneous tissue environments create spatial and temporal mismatches in drug exposure that can uncouple synergistic interactions, leading to unexpected treatment failure.
Objective: This study aims to develop a physiologically relevant in vitro model that integrates infection-site microenvironments and drug-specific pharmacokinetics.
Neuropathol Appl Neurobiol
October 2025
Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Târgu Mureș, Romania.
Aims: The clusterin (CLU) gene is genetically associated with Alzheimer's disease (AD), and CLU levels have been shown to positively correlate with regional Aβ deposition in the brain, including in arteries from cerebral amyloid angiopathy (CAA) patients. CLU has also been shown to alter the aggregation, toxicity and blood-brain barrier transport of amyloid beta (Aβ) and has therefore been suggested to play a key role in regulating the balance between Aβ deposition and clearance in both the brain and cerebral blood vessels. However, it remains unclear whether the role of clusterin in relation to Aβ deposition is protective or pathogenic.
View Article and Find Full Text PDFTranspl Int
September 2025
Unit for Heart Failure and Transplantation, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Cytomegalovirus (CMV) infection poses significant challenges in solid organ transplant (SOT) recipients, impacting graft outcomes, morbidity, and in some cases survival. The ESOT CMV Workshop 2023 convened European experts to discuss current practices and advances in the management of CMV with the aim of improving the quality of life of transplant recipients. Discussions covered crucial areas such as preventive strategies, diagnostic challenges, therapeutic approaches, and the role of cell-mediated immunity (CMI) monitoring.
View Article and Find Full Text PDFLipid nanoparticles (LNPs) are widely used in drug delivery due to their low toxicity, excellent biocompatibility, and ability to facilitate endosomal escape. A critical factor influencing the in vivo behavior of LNPs is the formation of a biomolecular corona (BC) on their surface. This layer of biomolecules affects key biological processes such as targeting, absorption, distribution, metabolism, and clearance.
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