The concentration of digoxin in blood was determined by the radio-immunologic method in 41 patients with circulatory insufficiency and permanent form of auricular fibrillation who were treated with the drug. In 85.5% of cases the therapeutic digoxin concentrations did not exceed 2 ng/ml. The therapeutic concentrations ranged from 0.3 to 3.6 ng/ml, the toxic from 0.9 to 6 ng/ml. A relationship was established between the dose of digoxin and its concentration in the blood of patients with normal renal filtration. It is concluded that the blood digoxin concentrations alone, without the clinical data being taken into account, cannot be a reliable criterion in assessment of the level of saturation with cardiac glycosides. Study of the dynamics of blood digoxin concentration in each patient allows its determination to be used to assess the tolerance to the drug, choose the adequate maintenance dose and the time for its correction, and to confirm the clinical signs of digitalis intoxication if the concentration of digoxin is above 2.5 ng/ml.
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Clin Pharmacol Drug Dev
January 2025
Clinical Pharmacology Modeling and Simulation, Amgen Inc., Thousand Oaks, CA, USA.
Sotorasib is a small-molecule Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C inhibitor indicated for the treatment of KRAS G12C-driven cancers. KRAS G12C is a common mutation in solid tumors, including non-small cell lung cancer. In vitro studies suggested that sotorasib is a weak inhibitor of P-glycoprotein transporter.
View Article and Find Full Text PDFClin Pharmacol Drug Dev
December 2024
Gossamer Bio, Inc., San Diego, CA, USA.
Seralutinib, an inhaled, small-molecule tyrosine kinase inhibitor in clinical development for the treatment of pulmonary arterial hypertension (PAH), was evaluated for its potential as a perpetrator or victim of a metabolic and transporter-based drug-drug interactions in 2 phase 1 studies. In study 1, 24 participants received a cocktail of probe substrates: caffeine (CYP1A2), montelukast (CYP2C8), flurbiprofen (CYP2C9), midazolam (CYP3A), and pravastatin (OATP1B1/1B3), plus digoxin (P-gp) with or without seralutinib. In study 2, 19 participants received seralutinib with/without itraconazole, a strong CYP3A inhibitor, or fosaprepitant, a weak CYP3A inhibitor.
View Article and Find Full Text PDFSemin Dial
December 2024
Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Extracorporeal therapies could be required for treatment of life-threatening severe acute intoxication. We present the case of an 82-year-old patient admitted to our Nephrology Unit because of metformin-associated lactic acidosis (MALA) and acute kidney injury (AKI stage III AKIN criteria). The patient also presented severe intoxication of digoxin and apixaban.
View Article and Find Full Text PDFAm J Vet Res
December 2024
Phantom Laboratory, Greenwich, NY.
Objective: The objective of this study was to satisfy the US FDA's Center for Devices and Radiological Health regarding the safety of targeted osmotic lysis (TOL), a novel treatment for advanced carcinomas, in Beagle dogs.
Methods: 12 intact Beagle dogs, 6 males and 6 females, were divided into 2 treatment groups of 6, each receiving 3 TOL cycles. For each 6-day cycle, digoxin was administered orally at 0.
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