Elimination theophylline

Drug/Food interactions Theophylline elimination is increased (half-life shortened) by a low carbohydrate, high protein diet, and charcoal broiled beef (due to a high polycyclic carbon content). Conversely, elimination is decreased (prolonged half-life) by a high carbohydrate low protein diet. Food may alter the bioavailability and absorption pattern of certain sustained-release preparations. Some sustained-release preparations may be subject to rapid release of their contents when taken with food, resulting in toxicity. It appears that consistent administration in the fasting state allows predictability of effects. 

Conrad KA, Nyman DW. Effects of metoprolol and propranolol on theophylline elimination. Clin Pharmacol Ther 1980 28(4) 463-7. 

Because of its mechanism of action, tacrine has the potential to interfere with the activity of anticholinergic medications. A synergistic effect is expected when tacrine is given concurrently with succinylcholine, cholinesterase inhibitors, or cholinergic agonists, such as bethanecol. Coadministration of tacrine with theophylline increases theophylline elimination half-life and average plasma concentrations. 

Angus, P.W. Ng, C.Y. Ghabrial, H. Morgan, D.J. Smallwood, R.A. Effects of chronic left ventriculeir failure on hepatic oxygenation and theophylline elimination in the rat. Drug Metab.Dispos., 1995, 23, 485-489... 

Theophylline elimination is predominantly mediated by hepatic metabolism. The liver metabolizes about 85 to 90% of the absorbed dose of theophylline the remainder is excreted unchanged by the kidneys. Therefore, dosage adjustments for renal failure are almost unnecessary. Moreover, the hepatic extraction ratio of theophylline is only 10%, indicating a negligible first-pass inactivation after oral administration. " ... 

Infectious Diseases. Prolonged fever may also slow theophylline elimination (up to 50% reduced Cl). ° Although the level and dnration of fever necessary for this effect is not known, fever must be sustained to resnlt in an appreciable theophylline accumulation. Although this is unlikely for fever lasting less than 24 h, dosage should be reduced in patients previously maintained within the therapentic range, if fever is high and sustained, e.g., >102°F for more than 24 h. 

Thiabendazole reduces theophylline elimination by more than 50% due to CYP isoenzymes inhibition.i3 ... 

Kelly, H. W., Powell, J. R., and Donohue, J. R, Ranitidine at very large doses does not inhibit theophylline elimination, Clin. Pharmacol. Ther., 39(5) 577-581, 1986. 

Gray JD, Renton KW, Hung OR. Depression of theophylline elimination following BCG vaccination. BrJ Clin Pharmacol ( 9S3) 16, 735-7. 

Conrad KA, Woodworth JR. OrciprenaUne does not alter theophylline elimination. BrJ Clin... 

Soto J, Sacristan JA, Alsar Ml. Diltiazem treatment impairs theophylline elimination in patients with bronchospasticair ray disease. Ther Drag Moral ( 99 16,49-52. 

Nielsen-Kudsk JE, Buhl JS, Johannessen AC. Verapamil-induced inhibition of theophylline elimination in healthy humans. Pharmacol Toxicol (1990) 66,101-3. 

Adebayo GI. Effects of equimolar doses of cimetidine and ranitidine on theophylline elimination. Biopharm DrugDispos 9Z9) 10, 77-85. 

A study in 5 patients with stable ehronic active hepatitis B and 4 healthy subjects found that 20 hours after being given a single 9- or 18-million unit intramuscular injection of interferon (recombinant human interferon alfa A), the clearance of theophylline (given as intravenous aminophylline) was approximately halved (range 33 to 81%) in 8 of the 9 subjects. The mean theophylline elimination half-life was increased from 6.3 to 10.7 hours (1.5 to sixfold increases). In the healthy subjects the theophylline clearances were noted to have returned to their former values 4 weeks after the study. ... 

May DC, Jarboe CH, Ellenbuig DT, Roe EJ, Karibo J. The effects of erythromycin on theophylline elimination in normal males. J Clin Pharmacol (1982) 22,125-30. 

Oosterhuis B, Jonkman JHG, Andersson T, Zuiderwijk PBM. No influence of single intravenous doses of omeprazole on theophylline elimination kinetics. J Clin Pharmacol (1992) 32, 470-5. 

The theophylline elimination rate constant after a single intravenous dose of aminophylline was found to be greater in hyperthyroid patients (0.155 h ) than in euthyroid (0.107 h ) or hypothyroid patients (0.060 h ) some other pharmacokinetic parameters were also changed. The authors concluded that thyroid dysfunction may modestly alter theophylline requirements. It is therefore also likely that drug-induced changes in the thyroid status, such as those caused by amiodarone, may also alter the amount of theophylline needed to maintain therapeutic levels. 

In vivo, induction by omeprazole translated into acceleration of caffeine demethylation by 40 mg of omeprazole [66]. However, as analyzed elsewhere [41], quantitative changes (an - 13% increase in exhalation of C02) were trivial. Omeprazole doses up to 80 mg failed to influence theophylline elimination kinetics [20]. A dose of 20 mg left the metabolism of phenacetin unchanged [67]. By contrast, both 30 and 60 mg of lanso-... 

Negative results with pantoprazole in this area are less than conclusive, since the interaction potential with theophylline has only been studied at a pantoprazole dose of 30 mg applied by 2-min injections [58], so that the period of liver exposure was lower than in the clinical setting. Even so, a nonsignificant decrease in elimination half-life by 10% was noted. Lansoprazole hastening of theophylline elimination appears inconsiderable from a practical point of view. More important are concerns over possible links between cancerogenesis and inducibility of lA isoforms. The ambiguities of this issue have been mooted previously. In the present context, it may suffice to emphasize that the 1A induction by PPIs is trivial in magnitude, probably transient and may even have positive aspects [41]. 

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