key: cord-0007749-s9ej0d3d
authors: Kolibash, Albert J.; Kramer, William G.; Reuning, Richard H.; Caldwell, James H.
title: Marked decline in serum digoxin concentrations during an episode of severe diarrhea()
date: 2006-09-19
journal: Am Heart J
DOI: 10.1016/s0002-8703(77)80225-1
sha: b307ce89afb6d6cde8aaec7bf2fd5f8ec858a6ff
doc_id: 7749
cord_uid: s9ej0d3d

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During the past several years numerous studies involving digoxin pharmacokinetics and bioavailability have been reported.l ~ However, relatively few studies have been directed to the actual mechanism of digoxin absorption and in particular to the influence of factors such as altered intestinal motility and transit time, 3 intestinal disease, 4-6 and the role of the enterohepatic circulationY. 8 From these studies it does seem apparent that disturbances of normal gastrointestinal function might well result in a significant alteration of digoxm bioavailability. We would like to report such a circumstance involving an individual who demonstrated profound differences in serum digoxin levels during an acute transient diarrheal illnesS.

A 24-year-old healthy male volunteer received four 0.25 rag. digoxin tablets (Lanoxin. Burroughs Welcome, Lot 022-1) as part of a more extensive study of digoxin absorption and pharmacokinetics. Three hours after ingesting the drug the patient developed repeated episodes of watery diarrhea which persisted throughou t the subsequent 24 hours. A total of 15 serial blood samples were drawn during the first 24 hours following which a single blood sample was obtained every 24 hours for three days. Six weeks .following this illness the patient Was restudied in a healthy state using the same protocol with tablets from the same lot. The serum digoxin concentrations were determined in duplicate using an 11~ radioimmunoassay (Schwarz/Mann) with the subject's digoxin-free control plasma serving as the blank for the standard curve done simultaneously with experimental samples. The resultant serum levels were plotted against time for both treatments (Fig. 1 ). Since the patient was involved in a larger study which involved intravenous administration of 1 mg, of digoxin, it was possible to calculate the absolute bioavailability of the tablets by the area under the curve method2 Although the time to reach peak serum levels did not differ, and the peak levels were similar~ the calculated absolute bioavailability O f the tablets:given when the patient developed diarrhea (16 per cent) was substantially less than when the drug was administered under normal circumstances (84 per cent). Despite the fact that this study involved only a single dose of digoxin, we feel that the magnitude of the observed effect suggests that diarrhea may be of clinical importance in patients taking digoxin on a chronic basis. Although the mechanism responsible for such a dramatic alteration of serum digoxin levels cannot be established from the study, it was clearly not a result Of vomiting or of incomplete ingestion of the tablets. Since the peak serum levels and peak times did not appreciably differ in the two studies, the initial absorption of digoxin prior to the development of diarrhea was probably normal. The pronounced difference following onset of diarrhea is suggestive of a profound increase in fecal elimination of the drug. Mechanisms which could explain these observed differences include more rapid elimination of undissolved drug from the gastrointestinal tract, altered intestinal permeability, increased secretion of digoxin into the gastrointestinal tract, and interruption of the enterohepatic circulation.

We report this observation to call attention to the fact that acute diarrhea appeared to have a marked influence upon serum digoxin levels and to point out the need for further studies to more fully elucidate the effects of gastrointestinal disturbances on digoxin elimination, particularly in the chronically digitalized patient. If confirmed by more extensive

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