Influence of gastric pH on digoxin biotransformation

Kalra, Jawahar; Ahmed, Mohamed; Kepkay, David L.; Barrowman, J. A.

doi:10.1038/clpt.1980.3

Cited by 26 publications

(10 citation statements)

References 2 publications

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“…The recovery of hydrolytic metabolites mainly after oral intake of digoxin is consistent with previous reports demonstrating intragastric hydrolysis of the glycoside (Beermann et al, 1972.;Gault et al, 1980). Also consistent with a previous study (Magnusson et al, 1982b) non-extractable metabolites, i.e.…”

Section: Discussionsupporting

confidence: 92%

Metabolism of digoxin after oral and intrajejunal administration.

Magnusson¹

1983

Brit J Clinical Pharma

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To study the influence of administration site on metabolism of digoxin in the gut, urinary excretion of digoxin and its metabolites was compared after oral and intrajejunal administration of [:3H]-digoxin solution to eight healthy volunteers, using liquid chromatography for the drug analysis. Dihydrodigoxin was not excreted in higher amounts after the more distal administration. The excretions of hydrolytic and non-extractable metabolites were significantly greater after the oral administration.

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Section: Discussionsupporting

confidence: 92%

Metabolism of digoxin after oral and intrajejunal administration.

Magnusson¹

1983

Brit J Clinical Pharma

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“…Several factors have been discussed that may affect the extent of digoxin absorption, such as changes in intragastric pH 27 and bacterial flora. 25 To avoid these gastrointestinal effects, we administered digoxin intravenously in this study.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Erythromycin and Clarithromycin on the Pharmacokinetics of Intravenous Digoxin in Healthy Volunteers

Tsutsumi¹,

Kotegawa²,

Kuranari³

et al. 2002

Journal of Clinical Pharmacology

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Several case reports have suggested an interaction between digoxin and macrolide antibiotics. The authors investigated the effect of erythromycin and clarithromycin on the pharmacokinetics of intravenously administered digoxin (0.5 mg) in healthy subjects. Nine male subjects participated in three studies (digoxin alone, digoxin with erythromycin, and digoxin with clarithromycin). Subjects took erythromycin (800 mg per day) or clarithromycin (400 mg per day) on the day before digoxin dosing and during the kinetic study, Neither of the macrolides affected serum digoxin concentration-time curves. However, more than 1.3-fold increases in urinary digoxin excretions were observed during erythromycin and clarithromycin coadministration compared with digoxin alone. There were significant differences in renal clearance between macrolide coadministration and the control condition (digoxin alone: 98.4 ml/min; digoxin with erythromycin: 137.3 ml/min; digoxin with clarithromycin: 133.6 ml/min). In conclusion, neither erythromycin nor clarithromycin has a significant effect on serum digoxin disposition after an intravenous administration. Renal digoxin excretion is not inhibited but rather enhanced by both macrolides.

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“…Solubility, dissolution rate, particle size, partition coefficient, pH, pK a , stability, gastrointestinal motility patterns, volume and flow rate of gastrointestinal contents, as well as membrane permeability have been found to influence drug absorption from the gastrointestinal tract. [1][2][3][4][5][6] It can be shown that the flux or the amount of drug transported per unit time and per unit area of the membrane is a function of the permeability of the drug and the concentration gradient across the gut and the systemic circulation. Maximum drug absorption occurs when the drug has maximum permeability and maximum concentration (saturation solubility) at the site of absorption.…”

Section: Introductionmentioning

confidence: 99%

Link between drug absorption solubility and permeability measurements in Caco-2 cells

Pade

Stavchansky

1998

Journal of Pharmaceutical Sciences

160

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The objective of this investigation was to establish a relationship between drug permeability and solubility in vitro and the extent of drug absorption in humans. We selected drugs with varying permeabilities and solubilities with the aim of establishing a relationship between permeability and solubility measurements in vitro and the extent of absorption in vivo. Effective permeability coefficients of the model drugs (naproxen, phenytoin, propranolol, diltiazem, salicylic acid, ephedrine, cimetidine, chlorothiazide, and furosemide) at 37 degrees C and pH 7.2 were estimated using the Caco-2 cell line. Saturation solubilities of the model drugs were estimated at pH 7.2 and at 37 degrees C. Data obtained from the permeability and solubility experiments were employed in classifying the drugs into high and low permeability-solubility groups. The permeability coefficients ranged from 1x10(-7) to 4x10(-5) cm/s, and a good correlation was observed between the permeability coefficients in Caco-2 cells and percent absorbed in humans. Drugs in the high permeability, high solubility class are completely absorbed (90% or higher). The study results indicate that there is a strong link between permeability measured in Caco-2 cells, solubility, and fraction of drug absorbed in humans.

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Influence of gastric pH on digoxin biotransformation

Cited by 26 publications

References 2 publications

Metabolism of digoxin after oral and intrajejunal administration.

Metabolism of digoxin after oral and intrajejunal administration.

The Effect of Erythromycin and Clarithromycin on the Pharmacokinetics of Intravenous Digoxin in Healthy Volunteers

Link between drug absorption solubility and permeability measurements in Caco-2 cells

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