title: Tissue distribution and elimination of digoxin and methyldigoxin after single and multiple doses in dogs.
abstract: Glycoside concentrations in plasma and various tissues of dogs were determined after a single and repeated intravenous administration of tritium-labeled digoxin and beta-methyldigoxin. Twenty-four hours after single dosing, the highest concentrations were measured in the kidney. This was followed by the heart, adrenal gland, liver, pancreas, lung, spleen, diaphragm, and skeletal muscle. The glycoside concentration in the brain was low after a single administration of dogoxin. A higher concentration was found after a single dose of the more lipophilic methyldigoxin. After repeated daily administration, the glycoside concentration in plasma and tissues increased continuously and, except for the brain, reached a plateau level after 6 to 8 days. The accumulation factor for both digoxin and methyldigoxin was 2.6. During daily administration for 10 days, the glycoside cconcentration in the brain increased continuously. The mean accumulation factor in all brain areas amounted to 12.4 for methyldigoxin. The concentration of digoxin and methyldigoxin in the tissues decreased, with mean half-lives of 33 and 28 hr, respectively. Glycoside elimination from the brain was clearly slower. A mean half-life of 73 hr was measured for digoxin and of 154 hr for methyldigoxin. The elimination of digoxin was largely renal, while that of methyldigoxin was largely fecal.
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D004077:Digoxin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism*; D004285:Dogs; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D008520:Medigoxin / Q000008:administration & dosage / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D004077:Digoxin; D008520:Medigoxin