Maximal intestinal absorption of digoxin, and its relation to steady state plasma concentration.

Johnson, B. F.; Bye, Carole

doi:10.1136/hrt.37.2.203

Cited by 41 publications

(25 citation statements)

References 13 publications

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“…Accordingly, high standards of tablet disintegration and dissolution have been required in order to achieve relatively high levels of biological availability (bioavailability), and of predictability and consistency of absorption, and in order to avoid clinical problems engendered by the use of poorly and variably absorbed preparations (Lindenbaum, Mellow, Blackstone & Butler, 1971;Shaw, Howard & Hamer, 1972). Even so, the bioavailability attained by modern digoxin tablets is only of the order of 63% (Johnson & Bye, 1975). Attempts have therefore been made to reduce the polarity of the digoxin molecule, without producing the very reduced renal clearance and prolonged half-life shown by digitoxin, by substituting non-polar groups in place of one or other hydroxyl groups on the tridigitoxose side chain.…”

Section: Introductionmentioning

confidence: 99%

Comparison of digoxin and medigoxin in normal subjects.

Hayward¹,

Greenwood²,

Hamer³

1978

Brit J Clinical Pharma

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I The properties of a recently introduced digitalis glycoside, 4-,-methyl digoxin (medigoxin)were compared to those of a standard digoxin preparation. Using a radioimmunoassay (RIA) technique, serial plasma levels were recorded for 8 h following a single oral dose in five fasting volunteer subjects, and urinary glycoside elimination was measured for 4 consecutive days after dosage by use of a modification of the RIA method. 2 It was found that this RIA was suitable for plasma level measurement of both digoxin and midigoxin by reference to appropriate standard curves. Comparison of the plasma level profiles of these two drugs showed that medigoxin was very rapidly absorbed with peak levels occurring within 15-30 min, while digoxin produced peak levels after 45-75 min. The area under the plasma level-time curve produced by medigoxin was also consistently greater than that produced by digoxin, even though the medigoxin dose used was smaller. Quantitative comparison of these areas after adjustment to compensate for differing doses showed that medigoxin is considerably more biologically available than digoxin under study conditions (ratio 1.6 + 0.25: 1), and comparison of quantitative urinary elimination suggested that medigoxin is eliminated in the urine to a lesser extent than digoxin and therefore it undergoes more metabolism and/or hepato-biliary elimination.

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Section: Introductionmentioning

confidence: 99%

Comparison of digoxin and medigoxin in normal subjects.

Hayward¹,

Greenwood²,

Hamer³

1978

Brit J Clinical Pharma

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“…Similar steady-state plasma concentrations after twice-daily ingestion of digoxin or ß-methyldigoxin tablets have been observed. 8 However, ß-methyldigoxin shows a slightly better absorption than does digoxin, 9 and the observed half-life of digoxin is somewhat shorter than that of ß-methyldigoxin. Finally, the elimination kinetics of ß-methyldigoxin and digoxin differ somewhat, apparently because of the higher renal clearance of digoxin.…”

Section: Discussionmentioning

confidence: 99%

Free and Total Digoxin in Serum During Treatment of Acute Digoxin Poisoning With Fab Fragments: Case Study

Eyer

Steimer²,

Müller³

et al. 2010

American Journal of Critical Care

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A woman ingested 10 mg of methyldigoxin in a suicide attempt and presented 19 hours after ingestion with clinical signs of glycoside intoxication. Her serum level of digoxin was 7.4 ng/mL, and antidotal therapy with Fab antibody fragments was started. The manufacturer's recommended dosing scheme was modified, with 80 mg Fab administered intravenously within 15 minutes followed by a continuous infusion at 30 mg/h. Total serum concentration of digoxin increased markedly within minutes after Fab therapy was started, while the level of free digoxin immediately decreased into the nontoxic range without recrudescent toxic effects of digoxin. The cumulative amounts of free and bound digoxin that were excreted in urine within 30 hours after ingestion were 900 µg and 1600 µg, respectively. Half-life of bound digoxin in urine was 9.9 hours; mean rate of clearance of bound digoxin in the urine was 7.0 mL/min. On the basis of these kinetic data, a smaller initial bolus dose of Fab followed by a continuous infusion may be a more tailored, cost-effective, and relatively safe therapy for patients who have overdosed on cardiac glycosides.

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“…Our results would therefore suggest that a solvent factor is responsible for the enhanced absorption of digoxin from this formulation. Previous studies from these laboratories demonstrated a greater extent of absorption of digoxin from paediatric elixir than from tablets of high dissolution rate (Johnson & Bye, 1975), and that hard gelatin encapsulation of a solid form of digoxin did not increase bioavailability (Johnson & Lader, 1974). Further studies of the effect of solvents on digoxin absorption may well be rewarding and might have wider applicability to other drugs which are incompletely absorbed.…”

Section: Discussionmentioning

confidence: 99%

Influence of soft gelatin on digoxin absorption.

O’Grady¹,

Johnson²,

Bye³

et al. 1978

Brit J Clinical Pharma

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1 The influence of encapsulation in soft gelatin on the absorption of digoxin from a solvent mixture of polyethylene glycol 400 90% W/W, ethanol 6% W/W, propylene glycol 3% W/W and water 1% W/W was studied in eight healthy volunteers. 2 Each volunteer received 0.6 mg digoxin as solution alone, as three intact capsules containing digoxin solution, as three capsules containing digoxin solution sectioned in half and as three capsules containing digoxin solution dissolved in water prior to administration. 3 There was no significant difference between the four treatments in terms of area under the plasma concentration‐time curves for 7 h, peak plasma concentrations, time to peak or in the cumulative urinary excretion for 6 days. 4 It is suggested that a constituent of the solvent rather than the presence of or encapsulation within soft gelatin may be the determining factor in enhanced absorption of digoxin from soft gelatin capsules as compared to aqueous solution or tablets of rapid dissolution rate.

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Maximal intestinal absorption of digoxin, and its relation to steady state plasma concentration.

Abstract: In a group of8 volunteers, peak plasma digoxin concentrations and areas under 8o-hour plasma concentration curves were significantly greater after i mg digoxin in paediatric elixir

Cited by 41 publications

References 13 publications

Comparison of digoxin and medigoxin in normal subjects.

Comparison of digoxin and medigoxin in normal subjects.

Free and Total Digoxin in Serum During Treatment of Acute Digoxin Poisoning With Fab Fragments: Case Study

Influence of soft gelatin on digoxin absorption.

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