Journal article
Food-Induced “Dose-Dumping” from a Once-a-Day Theophylline Product as a Cause of Theophylline Toxicity
Chest, Vol.87(6), pp.758-765
06/1985
DOI: 10.1378/chest.87.6.758
PMID: 3996063
Abstract
Three slow-release preparations of theophylline have received approval from the U.S. Food and Drug Administration (FDA) for “once-daily” dosing indications, amid controversy regarding the appropriateness of this decision. Because of specific concerns regarding data submitted to the FDA in support of the first of these products to be approved, Theo-24, we examined the absorption characteristics of this newly marketed formulation. Eight healthy volunteers received, in a crossover manner, single doses of a theophylline reference solution and Theo-24, taken both fasting and after a breakfast of bacon and eggs. The concentrations of theophylline were measured up to 60 hours after the dose. Absorption of Theo-24 after an overnight fast was very slow, with only 71 ± 6 percent (mean ± SE) of the dose ultimately absorbed. In contrast, food caused precipitous “dose-dumping,” resulting in dose-normalized peak levels in the serum that averaged 2.3 times higher than after a fasting dose. About half of the dose was absorbed in a four-hour period, generally beginning six to eight hours after the postprandial dose, and complete absorption was then attained within 24 hours (p<0.001). Toxic effects of theophylline occurred in four subjects when they took the dose with food whereas no toxic effects occurred during the fasting regimen. Consequently, doses of Theo-24 that would have attained a predicted peak concentration of 15μg/ml after multiple dosing taken without food would, if taken with food, have resulted in larger fluctuations and in peak concentrations in the potentially toxic range for six of the eight subjects.
Details
- Title: Subtitle
- Food-Induced “Dose-Dumping” from a Once-a-Day Theophylline Product as a Cause of Theophylline Toxicity
- Creators
- Leslie Hendeles - University of FloridaMiles Weinberger - University of IowaGary Milavetz - University of IowaMalcolm Hill - University of FloridaLeigh Vaughan - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Chest, Vol.87(6), pp.758-765
- Publisher
- Elsevier Inc
- DOI
- 10.1378/chest.87.6.758
- PMID
- 3996063
- ISSN
- 0012-3692
- eISSN
- 1931-3543
- Language
- English
- Date published
- 06/1985
- Academic Unit
- Pharmacy; Stead Family Department of Pediatrics; Pharmacy Practice and Science
- Record Identifier
- 9984365885902771
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