Influence of ranitidine on plasma metoprolol concentrations.

DeRuiter, Jack; Mitchard, M.; Smith, RobertN.

doi:10.1136/bmj.286.6383.2064-b

Cited by 5 publications

(1 citation statement)

References 6 publications

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“…Although there is some controversy (Spahn et al, 1983;Jack et al, 1983), it is widely held that drugs such as ranitidine and tiotidine, which do not possess an imidazole group, are less likely than cimetidine to produce important interactions at therapeutic doses (Henry et al, 1980;Serlin et al, 1981;Staiger et al, 1981).…”

Section: Introductionmentioning

confidence: 99%

Omeprazole: effects on oxidative drug metabolism.

Henry¹,

Somerville²,

Kitchingman³

et al. 1984

Brit J Clinical Pharma

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Omeprazole, a substituted benzimidazole, and a potent inhibitor of gastric parietal cell H+/K+ ATPase, was tested for drug interactions at two dose levels (30 mg and 60 mg/day) in man using the model drugs [14C]‐aminopyrine and antipyrine. Elimination of both models was assessed before and after 15 days treatment with omeprazole. In addition [14C]‐aminopyrine metabolism was assessed on day 2 of treatment to investigate the rapidity of onset of any effect. In 10 healthy male volunteers omeprazole 60 mg/day for 14 days prolonged aminopyrine 14CO2 half life (t1/2), measured on the 15th day, by 21% (P less than 0.05), and reduced percent dose demethylated in 2 h (ABT2) by 19% (P less than 0.005). No effect was seen on day 2 of therapy. After 14 days treatment antipyrine half‐life was prolonged by 10% (P less than 0.025) and clearance was reduced by 14% (P = 0.063). In nine healthy male volunteers omeprazole 30 mg/day for 14 days prolonged aminopyrine 14CO2 by 13% and reduced ABT2 by 11%. Both changes just failed to reach statistical significance. At this dose antipyrine metabolism was unaltered. As the dose of omeprazole used in clinical practice may be less than 30 mg/day it is unlikely that metabolic inhibition will occur during routine use, although it will be necessary to test for interactions with therapeutically more important compounds. Interactions should be looked for when large doses of omeprazole are being used to treat hypersecretory states.

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Section: Introductionmentioning

confidence: 99%

Omeprazole: effects on oxidative drug metabolism.

Henry¹,

Somerville²,

Kitchingman³

et al. 1984

Brit J Clinical Pharma

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Adverse Reactions and Interactions with H2-Receptor Antagonists

Penston

Wormsley

1986

Medical Toxicology

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Histamine H2-receptor antagonists have been used in the treatment of gastrointestinal diseases for more than a decade and during this period have become one of the most commonly prescribed groups of drugs in the world. The deserved popularity of the H2-receptor antagonists reflects, in part, their therapeutic efficacy, which has revolutionised the treatment of peptic ulcer disease. An equally, or more, important reason for the widespread use of H2-receptor antagonists is their remarkably low toxicity. We have attempted, in this review, to present a detailed account of the minor and more serious adverse reactions, while emphasising the low incidence of the former and the rarity of the latter. The toxicology of the H2-receptor antagonists is discussed under two main headings: adverse effects; and drug interactions. The latter category is potentially the more significant, since the frequent use of therapy with multiple drugs may give rise to drug interactions, some of which are serious and may even be lethal. These drug interactions occur especially in the gastrointestinal tract, the liver and the kidneys. Thus, the absorption of other drugs may be altered because the H2-receptor antagonists inhibit gastric secretion--an effect illustrated by ketoconazole, the absorption of which is reduced when given in combination with cimetidine. Very important drug interactions are caused by inhibition of the hepatic microsomal enzyme cytochrome P450 by some of the H2-receptor antagonists. This effect appears to be related to the chemical structure of the individual H2-receptor antagonists and is not attributable to histamine H2-receptor blockade. For example, cimetidine is a powerful inhibitor of cytochrome P450, while the interaction of ranitidine with this system is weaker. Consequently, cimetidine reduces the metabolism of many drugs which are normally degraded by phase I reactions, leading to potentially toxic plasma concentrations of therapeutic agents such as some oral anticoagulants, beta-blockers, anticonvulsants, benzodiazepines and xanthines. Some of the H2-receptor antagonists are actively secreted by the renal tubules and may thus compete with other drugs for cationic tubular transport mechanisms, resulting in reduced urinary excretion and hence potentially toxic plasma concentrations. This type of drug interaction has been reported after administration of both cimetidine and ranitidine with procainamide or quinidine.(ABSTRACT TRUNCATED AT 400 WORDS)

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