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A pharmacokinetic study of digoxin in the horse
Author(s) -
BRUMBAUGH GORDON W.,
THOMAS WILLIAM P.,
ENOS L. REED,
KANEKO JIRO J.
Publication year - 1983
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.1983.tb00460.x
Subject(s) - digoxin , pharmacokinetics , volume of distribution , bioavailability , oral administration , chemistry , elimination rate constant , serum concentration , half life , distribution (mathematics) , body weight , microgram , horse , pharmacology , medicine , endocrinology , in vitro , heart failure , mathematics , mathematical analysis , paleontology , biochemistry , biology
Digoxin was administered orally and intravenously to seven healthy adult mares and geldings in two separate trials. At a dose of 44 μg digoxin/kg body weight, the oral study was characterized by an absorption phase with a mean (± 1 standard deviation) peak serum digoxin concentration of 2.21 ng/ml (± 0.45) at a mean of 2.29 h (± 1.52) after administration. A second rise in serum digoxin concentration started about 6–8 h after administration and extended to about 20 h after administration. The mean bioavailability ( F ) was 23.38% (± 5.96). At a dose of 22 μg digoxin/kg body weight, the intravenous study was characterized by a two‐compartment model with the following mean pharmacokinetic measurements: distribution rate constant (α), 1.391 h ‐1 (± 0.1909); zero‐time serum digoxin concentration determined from the distribution phase ( A ), 21.247 ng/ml (± 5.6614); elimination rate constant (β), 0.0409 h ‐1 (± 0.0069); zero‐time serum digoxin concentration determined from the elimination phase ( B ), 3.82 ng/ml (± 0.433); apparent specific volume of distribution uncorrected for protein binding (V d β), 5.003 1/kg (± 0.5177). The mean β corresponded to a biological half‐life ( t 1/2 ±) of 16.9 h. Based upon results of this study, theoretically achievable steady‐state serum digoxin concentrations were calculated for maintenance doses given by oral and intravenous routes of administration with appropriate two‐compartment, multiple‐dose formulae. Loading doses were also calculated for each route. It is the opinion of the authors that the oral route of administration of digoxin is effective in the horse and may preclude the potential risks posed by the high serum digoxin concentrations immediately following intravenous administration.