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Update on the pharmacodynamics and pharmacokinetics of theophylline Hendeles L; Massanari M; Weinberger MChest 1985[Aug]; 88 (2 Suppl): 103S-111STheophylline has emerged as a major prophylactic agent for controlling the symptoms of chronic asthma, but it provides little if any relief of pulmonary symptoms caused by irreversible chronic airways obstruction. Although in vitro it inhibits phosphodiesterase and antagonizes adenosine receptors, theophylline's mechanism of action in asthma is unknown. Often, 10 to 20 micrograms/ml is used as the range of serum concentrations where there is the greatest likelihood of obtaining maximal benefit safely. Slow-release products have the potential to provide more stable serum concentrations with longer dosing intervals. However, clinically important differences in rate and sometimes extent of absorption exist between the 15 formulations sold under 29 brand names in this country. In patients with more rapid elimination, few products have sufficiently slow absorption to allow twice-daily use. Often these formulations must be administered every eight hours to prevent breakthrough in asthmatic symptoms despite promotional claims to the contrary. In patients with slower elimination, differences among products are unlikely to be clinically important with 12-hour dosing intervals. Current products approved for "once-a-day" dosing are clinically inadequate because of erratic absorption or excessive serum concentration fluctuations. Moreover, food induces dose dumping of potentially toxic amounts of theophylline from Theo-24, greatly increases the extent of absorption of theophylline from Uniphyl, decreases extent of absorption from Theo-dur-Sprinkle capsules, but has no clinically important effect on Theo-Dur tablets, Theobid, Slo-Bid, or Somophyllin-CRT. The effects of food or other factors that alter gastrointestinal physiology on theophylline absorption are unknown for most other products.|Asthma/blood/drug therapy[MESH]|Biotransformation[MESH]|Delayed-Action Preparations[MESH]|Drug Interactions[MESH]|Food[MESH]|Humans[MESH]|Intestinal Absorption[MESH]|Kinetics[MESH]|Liver/metabolism[MESH]|Lung Diseases, Obstructive/blood/*drug therapy/metabolism[MESH]|Metabolic Clearance Rate[MESH]|Theophylline/administration & dosage/analysis/metabolism/*pharmacology[MESH] |
