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Do SGLT2 Inhibitors Protect the Kidneys? An Alternative Explanation.
Endocr Metab Immune Disord Drug Targets
January 2025
Sheba Medical Center, Institute of Endocrinology, Tel-Hashomer, Israel.
SGLT2 inhibitors are a family of drugs that were developed to treat diabetes mellitus. In randomized controlled trials, SGLT2 inhibitors seem to prevent kidney deterioration in patients with nephropathies, both diabetic and non-diabetic. However, in contrast to biochemical/physiological results (proteinuria and serum creatinine levels) that improve in all studies, the clinical results (all-cause mortality, cardiovascular death, need for dialysis, or renal transplant) do not consistently improve.
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 PDFCASR, CLDN 14, ALPL & SLC34A1 genes are associated with the risk of nephrolithiasis in Egyptian children.
J Pediatr Urol
December 2024
Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt. Electronic address:
Backgrounds: The pathophysiology of nephrolithiasis is complex, influenced by both environmental and genetic factors. Calcium is the most prevalent metabolite present in the stone matrix. Stimulating the basolateral calcium sensing receptor (CASR) in the renal tubules leads to an increase in claudin-14 expression, reducing paracellular calcium permeability and increasing urinary Ca excretion.
View Article and Find Full Text PDFBackground: A new pathophysiologic approach to evaluating hyponatremic patients identified the different causes of hyponatremia, including non-hyponatremic patients with renal salt wasting (RSW). RSW was considered a rare to nonexistent syndrome until we found 24 (38%) of 62 hyponatremic patients in a general medical ward to have RSW. We induced RSW in rats by injecting plasma from 18 AD patients suspected to have RSW.
View Article and Find Full Text PDFUnravelling sources of variability on rocuronium pharmacokinetics: Implications for prolonged recovery in older patients.
Br J Clin Pharmacol
January 2025
Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics. College of Pharmacy, University of Florida, Orlando, FL, USA.
Aims: Residual neuromuscular blockade (RNB) commonly occurs when using neuromuscular blockers and increases the risk for pulmonary complications, such as airway obstruction and severe hypoxemia, in extubated patients. Rocuronium exhibits a high variability in recovery time, contributing to an increased risk for RNB. This study aimed to identify and characterize the sources of variability in rocuronium exposure and response via a population pharmacokinetic/pharmacodynamic (PK/PD) analysis and to apply the developed PK/PD model to investigate clinical implications.
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