RELATIONSHIP OF AGE TO THE METABOLISM AND PROTEIN-BINDING OF DIGOXIN IN SHEEP

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Abstract
The relationship of age to the protein binding and metabolism of digoxin was studied in newborn and adult sheep. Protein binding, studied by equilibrium dialysis, varied directly with albumin concentration. The percentage of digoxin bound to protein did not differ with age: 17.2 .+-. 1.2% in newborn lambs and 17.6 .+-. 1.7% in ewes. The percentage of drug bound did not change significantly over a concentration range of 0.5-5 ng/ml. Metabolic studies were performed by TLC on samples of serum, myocardium and urine obtained after animals were treated for 4 days with [3H]digoxin. In both newborns and adults more than 70% of digoxin remained unmetabolized. The mean metabolic composition of all 3 tissues for newborns and adults, respectively, was: digoxin-80.3%, 77.0%; digoxigenin bisdigitoxoside-9.6%, 12.5%; digoxigenin monodigitoxoside-6.4%, 7.0%; digoxigenin-3.7%, 3.5%. Apparently age-related differences in the effects of digoxin in sheep are not due to variations in drug binding or drug metabolism.