digoxin and Acidosis--Respiratory

Topics: Acidosis, Respiratory; Animals; Cymarine; Digoxin; Guinea Pigs; Heart; Hypoxia; In Vitro Techniques; Isoproterenol; Myocardial Contraction; Strophanthins

The aim of the present study was to investigate the influence of hypoxemia combined with respiratory acidosis on the kinetics of digoxin in conscious dogs. One group of three beagles was exposed to air and 7 days later to 10% O2, 10% CO2, and 80% N2. In a second group of three dogs, the order of exposure to the two atmospheric conditions was reversed. The dogs received 25 micrograms/kg digoxin and blood and urine samples were collected over the next 29 h. At the conclusion of the second treatment, the dogs were sacrificed to determine digoxin concentrations in the left ventricle, liver, renal cortex, and skeletal muscle. Digoxin total body clearance increased from 6.2 +/- 0.9 in control to 9.0 +/- 1.0 mL X min-1 X kg-1 in hypoxemic and hypercapnic dogs (p less than 0.05). The digoxin apparent volume of distribution at steady state (Vss) was increased in the dogs with hypoxemia and hypercapnia (11.63 +/- 1.11 vs. 8.62 +/- 0.41 L/kg in the controls, p less than 0.05). As a consequence the digoxin plasma half-life remained unchanged (18.6 +/- 1.5 h in hypoxemic and hypercapnic dogs versus 20.1 +/- 2.8 h in the controls). In dogs with hypoxemia and hypercapnia, the ratio of tissue to plasma digoxin concentrations tended to increase in the liver, in the renal cortex, and in the left ventricle and remained unchanged in the left hind leg muscle. In vitro studies showed that the digoxin total binding to erythrocyte membranes was slightly increased in the dogs with hypoxemia and hypercapnia, resulting from an increase in the apparent intrinsic association constant for digoxin (p less than 0.003). It is concluded that hypoxemia combined with respiratory acidosis changes digoxin disposition in the conscious dog and is the cause of a digoxin redistribution into the tissues.

Topics: Acidosis, Respiratory; Animals; Consciousness; Digoxin; Dogs; Erythrocyte Membrane; Hypoxia; Kinetics; Male; Tissue Distribution

The correlation between arterial blood pH and digoxin plasma levels was studied after digoxin (Eudigox) administration a) in a single p.o. dose, b) in a steady state p.o. regimen, or c) i.v. The clinical trial was carried out on 26 male hospitalized patients selected and divided into groups according to their arterial blood pH values, which ranged between 7.20 and 7.53. Arterial blood pH proved to be directly correlated with digoxin plasma levels and with the corresponding AUC and inversely with the total plasma clearance of the drug. The data may explain the strongly reduced activity shown by digoxin in patients suffering from respiratory acidosis in clinical practice.

Topics: Acidosis, Respiratory; Aged; Coronary Disease; Digoxin; Female; Humans; Hydrogen-Ion Concentration; Male; Middle Aged

Topics: Acetanilides; Acidosis, Respiratory; Alkalosis; Amino Alcohols; Animals; Bicarbonates; Blood Pressure; Cardiac Complexes, Premature; Cats; Digitoxin; Digoxin; Electrocardiography; Female; Guinea Pigs; Heart; Heart Atria; Heart Ventricles; Hydrogen-Ion Concentration; Male; Microelectrodes; Propylamines; Reserpine; Sodium; Strophanthins; Tromethamine

Topics: Acidosis, Respiratory; Age Factors; Arrhythmias, Cardiac; Cardiac Catheterization; Cardiomegaly; Cyanosis; Diagnosis, Differential; Digoxin; Dyspnea; Electrocardiography; Ethacrynic Acid; Heart Defects, Congenital; Heart Failure; Hemodynamics; Hepatomegaly; Humans; Infant; Infant Care; Infant, Newborn; Lung Diseases; Monitoring, Physiologic; Oxygen; Parenteral Nutrition; Radiography

Topics: Acidosis, Respiratory; Animals; Blood; Cats; Digitoxin; Digoxin; Hydrogen-Ion Concentration; Lethal Dose 50; Ouabain