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The canine blood-brain barrier in health and disease: focus on brain protection.
Vet Q
December 2025
Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada.
This review examines the role of the canine blood-brain barrier (BBB) in health and disease, focusing on the impact of the multidrug resistance (MDR) transporter P-glycoprotein (P-gp) encoded by the gene. The BBB is critical in maintaining central nervous system homeostasis and brain protection against xenobiotics and environmental drugs that may be circulating in the blood stream. We revise key anatomical, histological and functional aspects of the canine BBB and examine the role of the gene mutation in specific dog breeds that exhibit reduced P-gp activity and disrupted drug brain pharmacokinetics.
View Article and Find Full Text PDFDual EGFR and telomerase inhibitory potential of new triazole tethered Schiff bases endowed with apoptosis: design, synthesis, and biological assessments.
RSC Med Chem
December 2024
Department of Pharmaceutical Chemistry, College of Pharmacy, The University of Mashreq Baghdad 10023 Iraq.
Many cancers have displayed resistance to chemotherapeutic drugs over the past few decades. EGFR has emerged as a leading target for cancer therapy inhibiting tumor angiogenesis. Besides, studies strongly suggest that blocking telomerase activity could be an effective way to control the growth of certain cancer cells.
View Article and Find Full Text PDFMicrodose Cocktail Study Reveals the Activity and Key Influencing Factors of OATP1B, P-Gp, BCRP, and CYP3A in End-Stage Renal Disease Patients.
Clin Pharmacol Ther
January 2025
Drug Clinical Trial Center, Peking University Third Hospital, Beijing, China.
OATP1B, P-gp, BCRP, and CYP3A are the most contributing drug-metabolizing enzymes or transporters (DMETs) for commonly prescribed medication. Their activities may change in end-stage renal disease (ESRD) patients with large inter-individual variabilities (IIVs), leading to altered substrate drug exposure and ultimately elevated safety risk. However, the changing extent and indictive influencing factors are not quantified so far.
View Article and Find Full Text PDFPopulation Pharmacokinetic Modeling of Certepetide in Human Subjects With Metastatic Pancreatic Ductal Adenocarcinoma.
Clin Pharmacol Drug Dev
January 2025
Department of Pharmacometrics Modeling, A2-Ai LLC, Ann Arbor, MI, USA.
Certepetide (aka LSTA1 and CEND-1) is a novel cyclic tumor-targeting internalizing arginyl glycylaspartic acid peptide being developed to treat solid tumors. Certepetide is designed to overcome existing challenges in treating solid tumors by delivering co-administered anticancer drugs into the tumor while selectively depleting immunosuppressive T cells, enhancing cytotoxic T cells in the tumor microenvironment, and inhibiting the metastatic cascade. A population pharmacokinetic (PK) analysis was conducted to characterize the concentration-time profile of patients with metastatic exocrine pancreatic cancer receiving certepetide in combination with nab-paclitaxel and gemcitabine, and to investigate the effects of clinically relevant covariates on PK parameters.
View Article and Find Full Text PDFAdvancements in Transdermal Drug Delivery Systems: Harnessing the Potential of Macromolecular Assisted Permeation Enhancement and Novel Techniques.
AAPS PharmSciTech
January 2025
Department of Pharmaceutics, School of Pharmaceutical Science, Siksha 'O' Anusandhan University, Bhubaneswar, 751003, Odisha, India.
Transdermal drug delivery (TDD) represents a transformative paradigm in drug administration, offering advantages such as controlled drug release, enhanced patient adherence, and circumvention of hepatic first-pass metabolism. Despite these benefits, the inherent barrier function of the skin, primarily attributed to the stratum corneum, remains a significant impediment to the efficient permeation of therapeutic agents. Recent advancements have focused on macromolecular-assisted permeation enhancers, including carbohydrates, lipids, amino acids, nucleic acids, and cell-penetrating peptides, which modulate skin permeability by transiently altering its structural integrity.
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