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Assessment of the biologic availability of digoxin in man
Author(s) -
Fleckenstein Lawrence,
Kroening Bruce,
Weintraub Michael
Publication year - 1974
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1974163part1435
Subject(s) - digoxin , pharmacokinetics , medicine , pharmacology , crossover study , urine , heart failure , serum concentration , drug , therapeutic index , pathology , alternative medicine , placebo
Low serum digoxin levels were found in 8 institutionalized patients with congestive heart failure despite daily administration, in standard dosage, of a digoxin preparation for 4 weeks. All 8 patients developed serum levels within the accepted therapeutic range after receiving another digoxin preparation for 1 week. Analysis revealed that the first preparation did not meet USP reqUirements of content uniformity. In vitro testing demonstrated marked differences in dissolution characteristics between preparations. Large differences in the extent of availability were demonstrated in a single‐dose crossover study in 5 healthy volunteers. It was established that the pharmacokinetic data obtained from cumulative urinary excretion reflected differences in the area under the 8 hour serum digoxin curve during single‐dose studies and the postdistribution serum concentrations in multiple‐dose studies. Single‐dose studies with urine collections for 24 hours seem adequate to assess differences between formulations of digoxin tablets affecting biological availability and to develop correlation with in vitro dissolution tests.