Food induced changes in theophylline absorption from a once‐a‐day theophylline product.

Abstract

1 Bioavailability and the absorption pattern of theophylline from the sustained release theophylline (SRT) product, Uniphyllin, were studied in eight adults and eight children under fasting conditions in the morning, after a standardised breakfast in the morning, and under fasting conditions in the evening (adults only). Theophylline given intravenously was used as a reference.2 The extent of absorption of theophylline was complete for all administrations of SRT both in adults and children.3 In adults the absorption profiles after the three administrations of SRT were very similar and at no time point was there any difference in serum theophylline concentration or fraction absorbed between the three regimens. In addition, inter and intra individual variations in absorption were small. 4 In children food caused a substantial change in the absorption pattern of theophylline so that the profiles became rather unpredictable with delays in absorption and periods of rapidly increasing serum drug concentrations. In three of the patients the dose dumping phenomenon resulted in toxic serum drug concentrations. Dumping of the dose could take place at any time interval between 3 and 15 h post dosing. Cmax was about 50% higher after fed than after fasting medication (P < 0.01). 5 It is concluded that children should not take SRT in large doses in combination with food.

Predicting Food Effects on Drug Release from Extended-Release Oral Dosage Forms Containing a Narrow Therapeutic Index Drug

“…Depending on the type of dosage form and the intraluminal conditions, a co-administered meal can result in both so-called "positive" and "negative" food effects. Positive food effects typically come along with an increase in drug release from ER formulations and in the worst case, can represent a great risk for the patient, particularly when a large amount of the dose is dumped within a short period of time (22,23). Such positive food effects are often the result of the loss of the integrity of matrices or coatings (i.e., devices that control drug release of ER dosage forms).…”

Drug release from matrix tablets: physiological parameters and the effect of food

“…This can represent a great risk for the patient, especially in cases when a large amount of the dose is dumped within a short period of time [100,101]. Fats, high concentrations of bile components and pH changes [101,102] are typical triggers for increased drug-release rates.…”

“…This can represent a great risk for the patient, especially in cases when a large amount of the dose is dumped within a short period of time [100,101]. Fats, high concentrations of bile components and pH changes [101,102] are typical triggers for increased drug-release rates. These same factors can cause negative food effects for reasons such as adsorption of food contents, a decrease in luminal diffusivity due to an increase in viscosity in the upper GI tract and changes in the absorption rate due to food-induced changes in GI motility and passage time along the GI tract [103,104].…”

Once nightly sustained release theophylline in elderly subjects [letter]

“…Once nightly sustained release theophylline in elderly subjects A recent paper (Steffensen & Pedersen, 1986) has suggested that once nightly sustained release theophylline therapy (Uniphyllin, Napp Laboratories) produces 'very We have studied seven elderly patients (age 69-86, median 80 years) without asthma, in a rehabilitation unit, undergoing active rehabilitation for primarily musculoskeletal problems. None suffered from any significant systemic illness nor was taking any medication currently known to interfere with either absorption or elimination of theophylline.…”