Inhibition of digoxin absorption but not of digitoxin during cytostatic drug therapy.
Digoxin absorption is found to be decreased in patients with malabsorption syndromes on the basis of mucosal defects. Since intestinal mucosa can be damaged by cytostatic drugs, it was the purpose of these studies to investigate the influence of various cytostatic drugs on digoxin and digitoxin plasma levels and urinary excretion. In 9 patients with malignant lymphoma, who received 0.8 mg beta-acetyldigoxin (n = 6) or 0.5 mg digitoxin (n = 3) before and 24 h after combined therapy with cyclophosphamide, vincristine, procarbazine, and prednisone (CVPP) or cyclophosphamide, vincristine and prednisone (CVP), plasma glycoside concentrations were measured 0 to 8 h after digoxin and 0--168 h after digitoxin application and the areas under the plasma concentration-time curves were calculated. In 12 patients on 0.3 mg beta-acetyldigoxin and in 10 patients on 0.1 mg digitoxin, daily plasma glycoside concentrations and daily renal excretion were measured before and after CVPP, CVP or cyclophosphamide, vincristine, cytarabine and prednisone (CVAP) treatment schemes. The diminished steady-state plasma digoxin concentrations and daily renal glycoside excretion during the 24-168 h period after the cytostatic dose demonstrate a reversible impairment of digoxin absorption. In contrast cytostatic drug therapy does not lead to reduction in steady-state digitoxin plasma levels and daily renal glycoside excretion. The delayed time to peak after a single dose of digoxin or digitoxin during cytostatic drug therapy shows that rate of absorption of both glycosides is reduced. Our results indicate the need for very exact monitoring of digoxin dosage during cytostatic therapy. The use of digitoxin for these patients is an alternative in maintaining adequate digitalization.
D000970:Antineoplastic Agents / Q000494:pharmacology*; D004074:Digitoxin / Q000378:metabolism*; D004077:Digoxin / Q000378:metabolism*; D006027:Glycosides / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D007700:Kinetics
D000970:Antineoplastic Agents; D006027:Glycosides; D004077:Digoxin; D004074:Digitoxin