Theophylline absorption

Johansson, O., Lindberg, T., Melander, A., Wahlin-Boll, E., Different effects of different nutrients on theophylline absorption in man, Drug Nutr. Interact. 1985, 3, 205-211. 

Karim, A., Burns, T., Janky, D., and Hurwitz, A. Food-induced changes in theophylline absorption from controlled-release formulations II. Importance of meal composition and dosing time relative to meal intake in assessing changes in absorption. Clin. Pharmacol. Ther. 38 642—647, 1985. 

A. H. Staib, D. Loew, S. Harder, E. H. Grayl, and R. Pfab, Measurement of theophylline absorption from different regions of the gastrointestinal tract using a remote controlled drug delivery device, Eur. J. Clin. Pharmacol. 30 95-97 (1986). 

Food ordinarily slows the rate of theophylline absorption but does not limit its extent. With sustained-release preparations, food may decrease the bioavailability of theophylline with some products but may increase it with others. Recumbency or sleep also may significantly reduce the rate or extent of absorption. These factors make it difficult to maintain relatively constant concentrations of theophylline in plasma throughout the day. Concentrations required to alleviate asthmatic symptoms do not remain constant, and the emphasis has shifted toward designing dosing regimens that ensure peak concentrations in the early morning hours, when symptoms frequently worsen. 

Activated charcoal is effective in decreasing theophylline absorption from the gastrointestinal tract, and whole bowel irrigation is especially useful for decontamination of orally administered sustained-release formulations of the drug. Hypotension is often managed by saline infusion, though vasopressors may be required. The blood levels of theophylline are decreased by charcoal hemoperfusion or by hemodialysis. Ipecac fluid extract contains cardiotoxic alkaloids and should never be used as an emetic. The answer is (D). 

Intrasubject variability in the extent of absorption has also been described. The net result is large fluctuations in serum concentrations in some, but not aU dosing intervals, which may cause major problems in terms of interpretation of measured serum concentrations. - Similarly, diurnal variations in theophylline absorption with slower rates at night have to be taken into account. ... 

The steady-state peak serum theophylline concentration is a function of dose and dosing interval that are controlled by the respective health-care professional, and theophylline absorption rate and clearance determined by the dosage form used and the individual patient treated. Because rate and completeness of absorption vary for different formulations, only products with complete absorption should be preferred, especially if switching between formulations. The formulation selected should be capable of maintaining stable serum concentrations when taken no more often than twice daily. 

Fitzsimmons WE, Luskin SS, MacLeod CM, Luskin AT. Single-dose study of tiie effect of terfenadine on theophylline absorption and disposition.(1989) 62,213-14. 

It is believed that diltiazem and verapamil can, to a limited extent, decrease the metabolism of theophylline by the liver, possibly by inhibiting the cytochrome P450 isoenzyme CYP1A2. Similarly, nifedipine may alter hepatic theophylline metabolism, or it may increase the volume of distribution of theophylline. " Felodipine possibly reduces theophylline absorption. ... 

Sommers DK, Meyer EC, Van Wyk M, Moncrieff J, Sn3fman JR, Grim beek RJ. The influence of codeine, propantheline andmetoclopramide on small bowel transit and theophylline absorption from a sustained-release formulation. Br J Ctin Pharmacol (1992) 33, 305-8. 

A patient with chronic obstructive pulmonary disease had a 53% reduction in his serum theophylline levels accompanied by bronchospasm when he was fed continuously through a nasogastric tube with OsmoUte. The interaction occurred with both theophylline tablets (Theo-Dur) and liquid theophylline, but not when the theophylline was given intravenously as aminophylline. It was also found that the interaction could be avoided by interrupting feeding 1 hour either side of the oral liquid theophylline dose. Conversely, hourly administration of 100 mL of OsmoUte did not affect the extent of theophylline absorption from a slow-release preparation Slo-bid Gyrocaps) in healthy subjects, although the rate of absorption was slowed. Similarly, in healthy subjects, hourly administration of 100 mL of Ensure for 10 hours did not affect the rate or extent of absorption of theophylline from Theo-24 tablets. ... 

Gal P, La3Tson R. Interference with oral theophylline absorption by continuous nasogastric feedings. Ther Drug Monit(y9ZC) 8, 421-3. 

Bhargava VO, Sch LJ, BerlingerWG, Jungnickel PW. Effect of an enteral nutrient formula on sustained-release theophylline absorption. TherDn Momt(y9Z9) 11,515-19. 

Plezia PM, Thomley SM, Kramer TH, Armstrong EP. The influence of enteral feedings on sustained-release theophylline absorption. Pharmaco ierapy (1990) 10, 356-61. 

Bryson JC, Dukes GE, Kirby MG, Heizer WD, Powell JR. Effect of altering small bowel transit time on sustained release theophylline absorption. J Clin Pharmacol ( 9Z9) 29, 733-8. 

Cantral KA, Schaaf L J, Jungnickel PW, Monsour HP. Effect of sucralfate on theophylline absorption in healthy volunteers. ClinPharm (1988) 7, 58-61. 

Bouraoui, A., A. Toumi, H. Ben Mustapha, and J.L. Brazier. 1988. Effects of capsicum fruit on theophylline absorption and bioavailability in rabbits. Drug Nutr. Interact. 5(4) 345-350. 

Historically, the use of xanthines has been hampered by poor aqueous solubiUty, rapid but highly variable metaboHsm, and the existance of a low therapeutic index. SolubiUty problems were partially solved by the preparation of various salt forms, eg, aminophylline. However, it was since recognized that the added base in aminophylline only increases solubiUty by increasing pH and thus does not affect the rate of absorption from the gut (65). Thus, in more recent medical practice, theophylline is commonly dispensed in anhydrous form and aminophylline is only recommended for iv adrninistration. 

Use of the macrolides increases serum levels of digoxin and increases the effects of anticoagulants. Use of antacids decreases the absorption of most macrolides. The macrolides should not be administered with clindamycin, lincomycin, or chloramphenicol a decrease in the therapeutic activity of the macrolides can occur. Concurrent administration of the macrolides with theophylline may increase serum theophylline levels. 

Concurrent use of the fluoroquinolones with theophylline causes an increase in serum theophylline levels. When used concurrently with cimetidine, the cimetidine may interfere with the elimination of the fluoroquinolones. Use of the fluoroquinolones with an oral anticoagulant may cause an increase in the effects of the oral coagulant. Administration of the fluoroquinolones with antacids, iron salts, or zinc will decrease absorption of the fluoroquinolones. There is a risk of seizures if fluoroquinolones are given with the NSAIDs. There is a risk of severe cardiac arrhythmias when the fluoroquinolones gatifloxacin and moxifloxacin are administered with drains that increase the QT interval (eg, quini-dine, procainamide, amiodarone, and sotalol). 

There is a decreased absorption of lansoprazole when it is administered with sucralfate Lansoprazole may decrease tiie effects of ketoconazole, iron salts, and digoxin. When lansoprazole is administered with theophylline, there is an... 

This chapter describes use of solid-surface room temperature phosphorimetry (SSRTP) as a detection technique in the liquid chromatographic (LC) analysis of caffeine, theophylline, and theobromine. Measurements were made in a continuous mode, using a 2-nebulizer automatic system for SSRTP analysis (previously optimized for LC detection). Use of SSRTP and UV absorption detection was compared under identical experimental conditions.38... 

K Dackson, JA Stone, KJ Palin, WN Charman. Evaluation of the mass balance assumption with respect to the two-resistance model of intestinal absorption by using in situ single-pass intestinal perfusion of theophylline in rats. J Pharm Sci 81 321 — 325, 1992. 

Vashi, VI. and Meyer, M.C. (1988). Effect of pH on the in vitro dissolution and in vivo absorption of controlled-release theophylline in dogs. J. Pharm. Set 77 760-764. 

Van den Mooter, G., Samyn, C., and Kinget, R., In vivo evaluation of a colon-speeifie drug delivery system An absorption study of theophylline from eapsules eoated with azo polymers in rats, Pharm. Res., 12 244-247 (1995). 

Walton et al. (2001a) examined data for compounds eliminated by the cytochrome P450 isoenzymes CYP1A2 in humans. Absorption, bioavailabihty, and route of excretion were generally similar between humans and the test species for each of the substances (caffeine, paraxanthine, theobromine, and theophylline). However, interspecies differences in the route of metabolism, and the enzymes involved in this process, were identified. The magnitude of difference in the internal dose, between species, showed that values for the mouse (10.6) and rat (5.4) exceeded the fourfold default factor for toxicokinetics, whereas the rabbit (2.6) and the dog (1.6) were below this value. 

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. 

All new developments have a flip side. The availability of slow-release theophylline has produced new problems for toxicologists. In overdose theophylline is potentially lethal. When a poisoned patient arrives at hospital, a plasma concentration is measured and, for most drugs, it can reasonably be assumed that the absorptive phase would be nearing completion (or can be shortened by gastric aspiration or giving charcoal by mouth). No such... 

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