Ranitidine and cimetidine; drug interactions with single dose and steady‐state nifedipine administration.

Smith, S. R.; Kendall, M. J.; Lobo, Jessica; Beerahee, A; DeRuiter, Jack; Wilkins, Martin R.

doi:10.1111/j.1365-2125.1987.tb03050.x

Cited by 48 publications

(17 citation statements)

References 14 publications

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“…Several studies of cimetidine and nifedipine coadministration in healthy volunteers have confirmed this; cimetidine 800 or 1200 mg/day increased the AVC of nifedipine by 52 to 92% following single or multiple doses (Kirch et al 1983;Schwartz et al 1988;Smith et al 1987). There was no significant change in the time needed to attain tmax, suggesting that nifedipine absorption was unaltered.…”

Section: Calcium Antagonistsmentioning

confidence: 74%

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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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Section: Calcium Antagonistsmentioning

confidence: 74%

“…multiple dose regimens of nifedipine (Kirch et al 1983;Schwartz et al 1988;Smith et al 1987). Kirch et al (1983) also studied the pharmacodynamic effects of this interaction in a separate group of hypertensive patients; cimetidine significantly potentiated the hypotensive effect of nifedipine.…”

Section: Calcium Antagonistsmentioning

confidence: 97%

Clinical Relevance of Cimetidine Drug Interactions

Shinn

1992

Drug Safety

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“…Corresponding to this increase in the bioavailability of nifedipine caused by cimetidine, longer duration of changes in heart rate were observed in patients in the standing position. 33,34 These findings indicate that doses of nifedipine should be reduced by 50% when the drug is coadministered with cimetidine.…”

Section: Beta-adrenergic Blockersmentioning

confidence: 91%

Updates on Cytochrome P450-Mediated Cardiovascular Drug Interactions

Cheng

Frishman

Aronow

2009

American Journal of Therapeutics

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Cytochrome P (CYP) 450 is a superfamily of hemoproteins that play an important role in the metabolism of steroid hormones, fatty acids, and many medications. Many agents used for management of cardiovascular diseases are substrates, inhibitors, or inducers of CYP450 enzymes.When two agents that are substrates, inhibitors, or inducers of CYP450 are administered together, drug interactions with significant clinical consequences may occur. This review discusses CYP450-mediated cardiovascular drug interactions as well as noncardiovascular drug interactions that produced significant cardiovascular side effects. The principles in predicting drug interactions are also discussed.

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“…Nifedipine only modestly increases blood digoxin levels [46]. Cimetidine inhibits hepatic metabolism of nifedipine and increases blood levels [47]. Diltiazem also increases nifedipine levels [48].…”

Section: Dosage and Route O[ Administration Ni[edipine Capsulesmentioning

confidence: 98%

Calcium channel antagonists: part VI: Clinical pharmacokinetics of first and second-generation agents

Opie

1989

Cardiovasc Drug Ther

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A survey of the pharmacokinetic properties of the three prototypical calcium antagonist agents shows that they have in common a very high rate of hepatic first-pass metabolism with, in the case of verapamil and diltiazem, the formation of an active metabolite that affects the dose during chronic therapy. Therefore, the major factor altering the pharmacokinetic properties and the dose of the drug required is the capacity of the liver to metabolize the drug, which in turn depends on the hepatic blood flow and the activity of the hepatic metabolizing systems. Hence liver disease, a low cardiac output, and coadministration of certain drugs inducing or inhibiting the hepatic enzymes, all indirectly affect the pharmacokinetic properties of the calcium antagonists. There are also other potential drug interactions of a kinetic or dynamic nature that may arise. In general, renal disease has little effect on the pharmacokinetics of calcium antagonists.

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Ranitidine and cimetidine; drug interactions with single dose and steady‐state nifedipine administration.

Cited by 48 publications

References 14 publications

Clinical Relevance of Cimetidine Drug Interactions

Clinical Relevance of Cimetidine Drug Interactions

Updates on Cytochrome P450-Mediated Cardiovascular Drug Interactions

Calcium channel antagonists: part VI: Clinical pharmacokinetics of first and second-generation agents

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