Non-Interaction of Cimetidine With Digoxin Absorption

Jordaens, Luc; Hoegaerts, Jacques; Belpaire, Frans

doi:10.1080/22953337.1981.11718792

Cited by 17 publications

(7 citation statements)

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“…In an early study, Jordaens et al (1981) administered a single oral dose of digoxin 0.75mg to 8 subjects, who on a second occasion received cimetidine 400mg 10 hours before and 200mg 1 hour after digoxin administration. There were no alterations in digoxin absorption or disposition: in particular, the AUC up to 6 hours after dosing was unchanged.…”

Section: Digoxinmentioning

confidence: 99%

Pharmacokinetic Interactions of Cimetidine 1987

Somogyi

Muirhead

1987

Clinical Pharmacokinetics

185

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The number of studies on drug interactions with cimetidine has increased at a rapid rate over the past 5 years, with many of the interactions being solely pharmacokinetic in origin. Very few studies have investigated the clinical relevance of such pharmacokinetic interactions by measuring pharmacodynamic responses or clinical endpoints. Apart from pharmacokinetic studies, invariably conducted in young, healthy subjects, there have been a large number of in vitro and in vivo animal studies, case reports, clinical observations and general reviews on the subject, which is tending to develop an industry of its own accord. Nevertheless, where specific mechanisms have been considered, these have undoubtedly increased our knowledge on the way in which humans eliminate xenobiotics. There is now sufficient information to predict the likelihood of a pharmacokinetic drug-drug interaction with cimetidine and to make specific clinical recommendations. Pharmacokinetic drug interactions with cimetidine occur at the sites of gastrointestinal absorption and elimination including metabolism and excretion. Cimetidine has been found to reduce the plasma concentrations of ketoconazole, indomethacin and chlorpromazine by reducing their absorption. In the case of ketoconazole the interaction was clinically important. Cimetidine does not inhibit conjugation mechanisms including glucuronidation, sulphation and acetylation, or deacetylation or ethanol dehydrogenation. It binds to the haem portion of cytochrome P-450 and is thus an inhibitor of phase I drug metabolism (i.e. hydroxylation, dealkylation). Although generally recognised as a nonspecific inhibitor of this type of metabolism, cimetidine does demonstrate some degree of specificity. To date, theophylline 8-oxidation, tolbutamide hydroxylation, ibuprofen hydroxylation, misonidazole demethylation, carbamazepine epoxidation, mexiletine oxidation and steroid hydroxylation have not been shown to be inhibited by cimetidine in humans but the metabolism of at least 30 other drugs is affected. Recent evidence indicates negligible effects of cimetidine on liver blood flow. Cimetidine reduces the renal clearance of drugs which are organic cations, by competing for active tubular secretion in the proximal tubule of the kidney, reducing the renal clearances of procainamide, ranitidine, triamterene, metformin, flecainide and the active metabolite N-acetylprocainamide. This previously unrecognised form of drug interaction with cimetidine may be clinically important for both parent drug, and metabolites which may be active.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Digoxinmentioning

confidence: 99%

Pharmacokinetic Interactions of Cimetidine 1987

Somogyi

Muirhead

1987

Clinical Pharmacokinetics

185

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“…Furthermore, in 2 of the 11 patients, cimetidine increased digoxin concentrations. In contrast, other studies conducted in both patients and healthy volunteers have demonstrated that cimetidine had no effect on the Cmax, tmax, half-life, total or renal clearance, volume of distribution or urinary excretion of digoxin (Garty et al 1986;Jordaens et al 1981;Ochs et a1. 1984).…”

Section: Other Agentsmentioning

confidence: 86%

“…Monitor drug Choonara et al (1986); Hetzel et al levels, adjust (1979) Toon et al (1986Toon et al ( , 1987; Wallin et al (1979) No Pachon et al (1989); Puff et al (1989); Zylber-Katz (1988) No Fraley et al (1983); Garty et al (1986); Jordaens et al (1981); Ochs et al (1984) No Harvey et al (1984) No Gugler et al (1983) No Back et al (1988); Cate et al (1986); Dey et al (1983); Stockley et al (1986) Abbreviations: C = serum/blood/plasma drug concentration; AUC = area under the concentration-time curve; t'l2 = elimination halflife; CL = clearance.…”

Section: Theophyllinementioning

confidence: 98%

Clinical Relevance of Cimetidine Drug Interactions

Shinn

1992

Drug Safety

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The excellent efficacy and tolerability profiles of H2-antagonists have established these agents as the leading class of antiulcer drugs. Attention has been focused on drug interactions with H2-antagonists as a means of product differentiation and because many patients are receiving multiple drug therapy. The main mechanism of most drug interactions involving cimetidine appears to be inhibition of the hepatic microsomal enzyme cytochrome P450, an effect which may be related to the different structures of H2-antagonists. Ranitidine appears to have less affinity than cimetidine for this system. There have been many published case reports and studies of drug interactions with cimetidine, but many of these have provided pharmacokinetic data only, with little information concerning the clinical significance of these findings. Nevertheless, the coadministration of cimetidine with drugs that have a narrow therapeutic margin (such as theophylline) may potentially result in clinically significant adverse effects. The monitoring of serum concentrations of drugs coadministered with cimetidine may reduce the risk of adverse events but does not abolish the problem. However, for most patients, concomitant administration of cimetidine with drugs possessing a wide therapeutic margin is unlikely to pose a significant problem.

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“…A 24-h ECG recorded on the last day of both periods showed no significant difference in the frequency of ven- V/F = volume of distribution; CLF = total clearance; CLR = renal clearance with congestive heart failure [2], other investigations have not found any interaction [1,3,4,5]. It is concluded that co-administration of fl-methyldigoxin and ranitidine does not lead to a drug interaction.…”

Section: Tics Drug Interactionmentioning

confidence: 95%

“…During the 3-day period on fl-methyldigoxin, and the 7-day period on co-administered fl-methyldigoxin and ranitidine, serum digoxin concentrations were determined in blood collected each morning. On the day before ranitidine, and on the last day of the 7-day combined treatment period, the serum digoxin concentration was measured at 0, 1,2,3,4,5, 8, 12, and 24 h. The TDX immuno-fluorescence method was used throughout. Urine digoxin concentrations were measured in the 24-h urine collected each day.…”

mentioning

confidence: 99%

Lack of interaction ofβ-methyldigoxin with ranitidine in patients with chronic congestive heart failure

Enomoto

Kurasawa

Ichikawa

et al. 1992

Eur J Clin Pharmacol

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Antacids have been reported to impair the absorption of digoxin. However, a drug interaction between digoxin and H2-receptor antagonists, which control acid secretion, has not yet been well documented. Here, the effect of the Hereceptor antagonist, ranitidine, on the pharmacokinetics of digoxin in patients taking fl-methyldigoxin for chronic congestive heart failure is described.6 patients were studied, who were hospitalised for chronic congestive heart failure, and who were taking/3-methyldigoxin maintenance therapy (0.14).2 mg. day<). Their mean age was 75.2 (57-83) y and mean body weight 45.3 (36-66)kg. All patients had Class II heart failure (NYHA), and none had severe renal impairment.Ranitidine 150 mg b.i.d, was given for 1 week. During the 3-day period on fl-methyldigoxin, and the 7-day period on co-administered fl-methyldigoxin and ranitidine, serum digoxin concentrations were determined in blood collected each morning. On the day before ranitidine, and on the last day of the 7-day combined treatment period, the serum digoxin concentration was measured at 0, 1,2,3,4,5, 8, 12, and 24 h. The TDX immuno-fluorescence method was used throughout. Urine digoxin concentrations were measured in the 24-h urine collected each day. No concomitant drug treatment was changed.Ranitidine did not affect the serum digoxin concentrations in the 6 patients at steady-state (Fig.

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Non-Interaction of Cimetidine With Digoxin Absorption

Cited by 17 publications

References 0 publications

Pharmacokinetic Interactions of Cimetidine 1987

Pharmacokinetic Interactions of Cimetidine 1987

Clinical Relevance of Cimetidine Drug Interactions

Lack of interaction ofβ-methyldigoxin with ranitidine in patients with chronic congestive heart failure

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