Theophylline bioavailability

Food may also affect the integrity of the dosage form, causing an alteration in the release rate of the drug. For example, theophylline bioavailability from Theo-24 controlled-release tablets is much more rapid whengiven to a subject in the fed rather than fasted state (Fig. 6). 

Lin S. Studies on microencapsulation. 14. Theophylline bioavailability after single oral-administration of sustained-release microcapsules. Curr Ther Res Clin Exp 1987 41(4) 564-573. 

The effect of food on theophylline bioavailability is unclear. In general it appears that fat or fibre in food has no effect, whereas high-protein and high-carbohydrate diets decrease and increase the theophylline half-life, respectively. Significant changes in theophylline bio availability have been seen in patients given both enteral feeds and total parenteral nutrition. 

Gonzalez Straughn AB. Effect of meals and dosage-form modification on theophylline bioavailability from a 24-hour sustained-release delivery system. CUn Ther (1994) 16, 804-14. 

MN Gai, A Isla, MT Andonaegui, AM Thielemann, C Seitz. Evaluation of the effect of 3 different diets on the bioavailability of 2 sustained release theophylline matrix tablets. Int J Clin Pharmacol Ther 35 565-571, 1997. 

Theophylline is a narrow therapeutic index drug with significant difference in bioavailability following oral administration. The half-life of the drug is increased by heart failure, cirrhosis and viral infections, in elderly patients, and by certain drugs, such as cimetidine, ciprofloxacin, oral contraceptives and fluvoxamine. The half-life is decreased in smokers, chronic alcoholism, and by certain drugs, such as phenytoin, rifampicin and carbamazepine. 

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. 

Specific studies include the use of sorbitol with solutions of ampicillin [45], (Z,)-ascorbic acid [46], and amoxicillin [47]. It has also been found to influence the bioavailability of theophylline when compared to water [48]. 

Blood samples were taken at 0.25, 0.5, 1.5, 2.5, 4.5, 6.5, 8.5, 10.5 and 12.5 h and the concentration of theophylline in serum was assayed by a spectrophotometric method [7]. The samples were analysed in duplicate. Bioavailability was calculated from the area under the concentration curve following the trapezoidal rule. 

Erythromycin metabolites can inhibit cytochrome P450 enzymes and thus increase the serum concentrations of numerous drugs, including theophylline, oral anticoagulants, cyclosporine, and methylprednisolone. Erythromycin increases serum concentrations of oral digoxin by increasing its bioavailability. 

Poly(vinyl alcohol)-gel spheres with chitosan (PVA-GS/Ch) or without chitosan (PVA-GS) were prepared to control the GI transit time of drugs, and their particles were 5-10 pm [26]. PVA-GS/Ch displayed a longer small-intestinal transit time than PVA-GS. The transit rate was considered to decrease by the adhesion of chitosan to the intestinal mucus layer. PVA-GS/Ch and PVA-GS were loaded with theophylline and ampicillin. These released the drugs in a similar manner. The drugs were released almost completely at 4 h after the start of the release test. Both the gel spheres containing theophylline exhibited a bioavailability similar to that of the theophylline solution. Also, the bioavailability of ampicillin was greater in PVA-GS/Ch than in the PVA-GS and ampicillin solution the bioavailability of PVA-GS/Ch was approximately 150% of that of ampicillin solution (Table 3.2). As theophylline is rapidly absorbed in... 

Decreased bioavailability of digoxin, theophylline, cyclosporin, and phenprocoumon takes place when these drugs are combined with St. John s wort. 

ACE inhibitor Theophylline Chili pepper (Capsicum spp.) Cough Capsaicin depletes substance P Increased absorption and bioavailability... 

AZITHROMYCIN, CLARITHROMYCIN, ERYTHROMYCIN THEOPHYLUNE 1. t theophylline levels 2. Possibly i eiythromycin levels when given orally 1. Inhibition of CYP2D6-mediated metabolism of theophylline (macrolides and quinolones -isoniazid not known) 2.1 bioavailability uncertain mechanism 1. Monitor theophylline levels before, during and after co-administration 2. Consider an alternative macrolide... 

THEOPHYLLINE GRAPEFRUIT JUICE Possibly 1 efficacy Unclear. 1 bioavailability (significant from 1-4 hours) Avoid concomitant intake if slow-release theophylline preparations are used. Monitor levels and clinical state weekly if the intake of grapefruit is altered... 

High-protein diets decrease the bioavailability of theophylline (high-carbohydrate diets increasing the bioavailability of theophylline) and reduce the effects of levodopa and methyldopa (from competition of amino acids for absorption),... 

Disposition in the Body. Rapidly absorbed after oral administration bioavailability almost 100%. Metabolic reactions include V-demethylation and oxidation to uric acid derivatives. About 85% of a dose is excreted in the urine in 48 hours with up to 40% of the dose as 1-methyluric acid, 10 to 15% as 1-methylxanthine and up to 35% as 5-acetylamino-6-formylamino-3-methyluracil and 5-acetylamino-6-amino-3-methyluracil other metabolites excreted in the urine include theophylline, 1,7-dimethylxanthine (paraxanthine), 7-methylxanthine, and 1,3-dimethyluric acid. Less than 10% is excreted in the urine as unchanged drug. The extent of V-acetylation is genetically determined. Caffeine, theophylline, theobromine, and paraxanthine are found in plasma from dietary sources especially coffee, tea and cocoa. An average cup of coffee or tea contains approximately 100 mg of caffeine. 

Drugs that meet one or more of the criteria given above and have been shown to exhibit significant differences in the bioavailability of marketed dosage forms include digoxin, quinidine, furosemide, nitrofurantoin, prednisone, chloramphenicol, theophylline, chlorpromazine, phenytoin, amitriptyline, and phenylbutazone. 

For a few drugs such as theophylline, saliva drug concentrations have been employed to supplement the collection of blood samples. However, the intersubject and intrasubject variability in saliva/plasma ratios have generally precluded the sole use of saliva drug concentrations to assess bioavailability. For some drugs such as cephalosporin antibiotics, clinical studies may also include a determination of appearance of drug in other body fluids such as the cerebrospinal fluid and bile. 

Most medications have shorter half-lives in children than in adults, and therefore children may need sustained-release products to maintain serum concentrations in the therapeutic range. For example, a sustained-release theophylline product may be needed for a child with asthma. It may need to be administered every 8h to the child as compared to every 12 h for a healthy, non-smoking adult to maintain therapeutic serum concentrations. When choosing a sustained-release theophylline preparation for a child, it must be remembered that because of differences in release properties, theophylline sustained-release products are not interchangeable. A product selected for the pediatric asthma patient should be reliably absorbed with a minimal serum concentration variation and not a preparation that has exhibited a difference in bioavailability when administered with or without food.[ > - ]... 

Sagara, K. Kawata, M. Mizuta, H. Shibata, M. Utility of gastrointestinal physiology regulated-dogs Bioavailability study of a commercial sustained-release dosage form of theophylline. Biol. Pharm. Bull. 1994,17 (7), 931-934. 

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