Influence of hypoxemia and respiratory acidosis on the plasma kinetics and tissue distribution of digoxin in the conscious dog

Abstract

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 μg/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 min−1 kg−1 in hypoxemic and hypercapnic dogs (p < 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 < 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 < 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.