Effect of cisapride and metoclopramide on digoxin bioavailability

Kirch, Wilhelm; Janisch, H. D.; Santos, S. R.; Dührsen, Ulrich; Dylewicz, Piotr; Ohnhaus, E. E.

doi:10.1007/bf03189108

Cited by 29 publications

(10 citation statements)

References 4 publications

(1 reference statement)

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“…rate and extent of absorption of cyclosporin increased by 29% following a single dose of oral metoclopramide in renal transplant recipients [ 156]) or reduced (e.g. extent of absorption of digoxin in tablet form reduced when administered under steady-state conditions to healthy individuals [ 157]). To emphasise the formulation dependence of these observations, the extent of absorption of digoxin in tablet, but not capsule, form is reduced by coadministration of metoclopramide.ll27] These effects are presumably due to differences in dispersion of the drug as well as changes in intestinal transit.…”

Section: Prokinetic Agentsmentioning

confidence: 99%

Pharmacokinetic Considerations in Gastrointestinal Motor Disorders

Hebbard

Sun

Bochner

et al. 1995

Clinical Pharmacokinetics

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Although it has been recognised that alterations in gastrointestinal motility, whether induced by physiological or pathological processes, have significant effects on the pharmacokinetics of orally administered drugs, this subject has received inappropriately little attention. Studies relating to this topic have focused on healthy volunteers and animals and have largely been confined to the effects of single drug doses. There is limited information about the effects of disease on pharmacokinetics under steady-state conditions. Changes in gastrointestinal motility may affect the pharmacokinetics of orally administered drugs by altering the rate of delivery, bioavailability or mucosal absorption of the drug. In general the rate of absorption and time taken to achieve maximal plasma concentrations for well absorbed drugs may be modified by changes in gastrointestinal motility, but overall bioavailability is not usually affected. In these cases the therapeutic and clinical effects of the alteration in pharmacokinetics will, therefore, depend on which parameters are important for the action of the drug. For poorly absorbed drugs both the rate of absorption and bioavailability are likely to be altered by changes in gastrointestinal motility. However, the complex effects of food and disease, as well as the properties and formulation of any drug (solubility, ease of dispersion, delayed release formulation) often make the prediction of the magnitude, or even the direction, of any effect difficult to predict. Drugs with direct effects on gastrointestinal motility may influence their own patterns of absorption. In patients with gastrointestinal motility disorders, drugs administered in a controlled release formulation, or those with poor bioavailability, are most likely to have a poorly predictable therapeutic effect. Care should be taken to ensure that the formulation of the drug, its timing of administration in relation to meals and the use of coadministered drugs optimise, or at least ensure consistent absorption.

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Section: Prokinetic Agentsmentioning

confidence: 99%

Pharmacokinetic Considerations in Gastrointestinal Motor Disorders

Hebbard

Sun

Bochner

et al. 1995

Clinical Pharmacokinetics

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“…The effect of oral cisapride lOmg 3 times daily and metoclopramide IOmg 3 times daily on the absorption of oral digoxin 0.25mg twice daily for 7 days in 6 healthy young volunteers has been studied.l 15 However, careful examination of the alcohol concentration during the time most likely to affect psychomotor performance (30 to 60 minutes) revealed a significant interaction with cisapride, alcohol concentrations rising more rapidly in the alcohol + cisapride group than with alcohol alone (0.19 vs 0.11 glL/h, P < 0.05). The performance of a number of psychomotor tests was unaffected.…”

Section: Digoxinmentioning

confidence: 99%

Cisapride

Bedford

Rowbotham

1996

Drug Safety

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Cisapride is a prokinetic agent which restores motility of the gastrointestinal tract in conditions of decreased bowel transit. It may also alter the absorption of coadministered drugs. The absorption of morphine, diazepam, cyclosporin, alcohol (ethanol) and levodopa are increased. Initial absorption of cimetidine and raniditine is also increased, but overall absorption is lower due to increased bowel transit. The absorption of digoxin, propranolol and the anticoagulants warfarin and phenprocoumon appears unaffected by cisapride, although increase thrombotest values were seen with acenocoumarol (nicoumalone). Drug interactions leading to increased plasma concentrations of cisapride may produce an increase in adverse effects. The most important of these is QT interval prolongation and ventricular arrhythmias. Phenytoin does not appear to affect protein binding of cisapride. Cisapride metabolism is inhibited by the antifungals ketoconazole, fluconazole, itraconazole and miconazole, and by the antibacterials erythromycin, troleandomycin and clarithromycin. Cisapride should not be coadministered with these drugs. Cimetidine produces a small increase in cisapride plasma concentrations, which may be due to inhibition of metabolism. Cisapride absorption is unaffected by other antacids. Atropine may reverse the cisapride-induced increase in peristalsis. Prescribers should remain vigilant to the presence of these and other, as yet unreported, reactions.

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“…Cisapride also increased the initial rate of absorption of diazepam by enhancing gastric emptying (5). However, the gastrointestinal absorption of digoxin was reduced by cisapride, although the time required to reach the peak plasma concentration was not altered (6).…”

Section: Discussionmentioning

confidence: 92%

“…Therefore, gastric absorption might be decreased and absorption from the small intestine would be enhanced by cisapride (3). Interactions between cisapride and cimetidine, diazepam, and digoxin have been investigated previously (4)(5)(6). Cisapride shortened the time to peak plasma concentration and enhanced the gastrointestinal absorption of cimetidine (4).…”

Section: Discussionmentioning

confidence: 99%

Influence of Cisapride on the Pharmacokinetics and Antihypertensive Effect of Sustained-Release Nifedipine.

et al. 1996

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To investigate the clinical significance of interactions between cisapride and sustained-release nifedipine, we comparedthe plasma nifedipine concentration and blood pressure after administration of nifedipine alone (20 mg) with those obtained after administration of nifedipine with cisapride (2.5 mg) in 20 patients with hypertension. The plasma nifedipine level was not altered by cisapride at one hour after administration, but was significantly increased at two (p<0.01), three (p<0.01), and four (p<0.05) hours when compared with the level measured after nifedipine alone. Cisapride significantly decreased the mean blood pressure at three hours (p<0.05) after administration ofnifedipine. The acetaminophen method was used to determine gastric emptying time. The plasma concentration of acetaminophenat 45 minutes after administration was significantly increased by cisapride, suggesting that enhanced gastrointestinal motility might be the basis for the increase in the plasma nifedipine concentration. These results suggest that enhancement of the antihypertensive effect ofnifedipine can occur when the drug is prescribed with cisapride, and that caution is needed whenusing such a combination therapy. (Internal Medicine 35: 941-945, 1996)

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Effect of cisapride and metoclopramide on digoxin bioavailability

Cited by 29 publications

References 4 publications

Pharmacokinetic Considerations in Gastrointestinal Motor Disorders

Pharmacokinetic Considerations in Gastrointestinal Motor Disorders

Cisapride

Influence of Cisapride on the Pharmacokinetics and Antihypertensive Effect of Sustained-Release Nifedipine.

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