title: Treatment of asthma by a controlled-release theophylline tablet formulation: a review of the North American experience with nocturnal dosing.
abstract: As many as 80 percent of asthmatics experience nighttime or early-morning episodes, which are difficult to treat and potentially fatal. The greater-than-normal amplitude of circadian airflow variation in many asthmatics contributes heavily to the genesis of the early 'morning dip'. Beta-agonists and corticosteroids are of limited usefulness in nocturnal asthma, and slow-release theophylline drugs, while potentially effective, vary in 24-hr blood profile and hence their influence on nocturnal episodes. Traditional 12-hr 'symmetric' theophylline regimens, instead of meeting increased nocturnal demands, may actually produce lower night- than daytime blood levels. On the other hand, appropriately timed administration of a once-daily theophylline drug might provide maximum blood levels when needed and help stabilize 24-hr airflow. Accumulated data, summarized in this review, demonstrate the chronotherapeutic potential of single-daily evening doses of a controlled-release theophylline preparation (Uniphyl 400-mg tablets) in nocturnal and early morning asthma. Nighttime blood concentrations with this regimen were higher than were those with Theo-Dur tablets, B.I.D., in the same total daily doses, or with once-daily morning Uniphyl administration. In fed and fasted subjects, evening administration of Uniphyl 400-mg tablets was well tolerated and did not lead to 'dose dumping.' Clinically, this treatment demonstrated advantages over B.I.D. theophylline, over single-daily morning regimens, and over prior theophylline therapy. Advantages of the evening regimen included better early-morning airflow (without significant decline later in the day), more effective symptom control, better patient acceptance, fewer night awakenings, and the obvious convenience of once-daily dosing. In addition, lung function showed greater stability, throughout the day, with once-daily evening therapy than with traditional 12 hr dosing. Uniphyl 400-mg tablets may be administered once daily to provide maximum blood levels at the time of peak bronchoconstriction, whether at night or during the day.
authors.affiliation: Medical Department, Purdue Frederick Company, Norwalk, CT 06856.
authors.forename: P D
authors.initials: PD
authors.lastname: Goldenheim
authors.forename: E A
authors.initials: EA
authors.lastname: Conrad
authors.forename: L K
authors.initials: LK
authors.lastname: Schein
mesh_terms: D001249:Asthma / Q000097:blood / Q000188:drug therapy*; D002940:Circadian Rhythm; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D006801:Humans; D009656:North America; D013806:Theophylline / Q000008:administration & dosage* / Q000097:blood
chemical_list: D003692:Delayed-Action Preparations; D013806:Theophylline