Cimetidine impairs the elimination of theophylline and antipyrine

Roberts, Rosemary; Grice, Jeffrey E.; Wood, Laurence J.; Petroff, Victor; McGuffie, Christine

doi:10.1016/0016-5085(81)90647-8

Cited by 126 publications

(24 citation statements)

References 15 publications

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“…A recent case report indicated that theophylline half-life was increased, producing theophylline serum concentrations twice those expected." This case report supported the study of normal volunteers, by Jackson et al, which recorded a 39 percent decrease in theophylline clearance after cimetidine administration (300 mg q6h for 2 d).47 Comparable data were recorded by Roberts et al 48 Reitberg et al found that cimetidine can decrease theophylline clearance on the first day of cimetidine treatment in normal volunteers. "…”

Section: Pharmacokinetic Drug Interactionssupporting

confidence: 83%

A Practical Guide to Interactions Involving Theophylline Kinetics

McElnay¹,

Smith²,

Helling³

1982

Drug Intelligence & Clinical Pharmacy

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A practical guide to the drug interactions involving theophylline kinetics is presented. The text is classified into three categories--pharmacokinetics, pharmacodynamics, and miscellaneous drug interactions. In the discussion of pharmacokinetics, interactions are classified according to site; in vitro, intestinal, metabolic, protein binding, and renal mechanisms are considered. The pharmacodynamic section concentrates on possible additive effects of theophylline and other commonly used bronchodilators, while in the miscellaneous section, discussion is devoted to those interactions involving allergic skin testing and changed results of commonly used assay methods for theophylline. Increased awareness of possible interactions should lead to a more critical approach to theophylline prescribing, particularly in those cases where an unexpected therapeutic effect (or theophylline serum concentration) is obtained during the treatment of asthmatic patients.

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Section: Pharmacokinetic Drug Interactionssupporting

confidence: 83%

A Practical Guide to Interactions Involving Theophylline Kinetics

McElnay¹,

Smith²,

Helling³

1982

Drug Intelligence & Clinical Pharmacy

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“…Phenacetin was used as the-internal standard for antipyrine assays and extraction performed in an alkaline medium using 5 N NaOH (Roberts et al 1981). All serum samples and standards were assayed in duplicate.…”

Section: Methodsmentioning

confidence: 99%

The Effect of Smoking on Caffeine Elimination: Implications for Its Use as a Semiquantitative Test of Liver Function

Murphy¹,

McIvor²,

Yap³

et al. 1988

Clin Exp Pharma Physio

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1. The effects of caffeine ingestion and cigarette smoking on caffeine and antipyrine pharmacokinetics were studied using normal subjects as their own controls before and after cessation of smoking in an attempt to minimize genetic and other environmental influences. 2. Moderate caffeine ingestion had no inducing effect on caffeine or antipyrine clearance. 3. Cessation of cigarette smoking significantly reduced clearance of caffeine and antipyrine. 4. These results demonstrate that cigarette smoking significantly affects caffeine pharmacokinetics and this may contribute to the variable results for caffeine kinetics found in patients with liver disease.

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“…The results can be summarised by stating that this is an important, clinically significant interaction, of which the prescriber must be aware, and take appropriate action to avoid theophylline toxicity. (Table IV) When theophylline was given as a single intravenous dose to non-smokers, and then combined with cimetidine in doses ranging from 1.2 to 2.4g per day, theophylline clearance decreased by an average of 21% (Roberts et al 1981), 39% , 25% (Schwartz et al 1982), 35% (Breen et al 1982), 12% (Grygiel et al 1984), 39% and 31 % (Cusack et al 1985). Similarly, when single oral doses of theophylline were used the clearance was decreased by 30% (Reitberg et al 1981) and26% (Cohen et al 1985), and when long term administration oftheophylline was employed the clearance decreased by an average of 28% (Mulkey et al 1983), 29% (Lalonde et al 1983) and 12% (Grygiel et al 1984).…”

Section: Theophylline (13 Oimethylxanthine)mentioning

confidence: 97%

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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Cimetidine impairs the elimination of theophylline and antipyrine

Cited by 126 publications

References 15 publications

A Practical Guide to Interactions Involving Theophylline Kinetics

A Practical Guide to Interactions Involving Theophylline Kinetics

The Effect of Smoking on Caffeine Elimination: Implications for Its Use as a Semiquantitative Test of Liver Function

Pharmacokinetic Interactions of Cimetidine 1987

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