Once-a-day dosing with theophylline: a comparison of four sustained-release products

This study compared once-a-day dosing of Slo-bid, Theo-Dur, Theo-24 and Uniphyl, sustained release theophylline preparations, in the treatment of 12 mild to moderate asthmatic patients (FEV1 greater than 60%). Eight hundred milligrams was given once-a-day in the morning for 2 weeks for each drug in this 4-way, crossover, open-label study. At the end of each 2-week period, pharmacokinetics were assessed by measuring theophylline levels every two hours for 24 hours. Efficacy was evaluated by spirometry, physical examination, daily peak flow measurements, and daily symptom diaries. In an additional 2-week period, Slo-bid 800 mg, was taken once-a-day after the evening meal and the same measures of pharmacokinetics and efficacy were performed. Slo-bid (range 8.8, coefficient variation 19.5) exhibited significantly less intrapatient variability than Theo-Dur (range 12.2, coefficient of variation 36.5) and Theo-24 (range 8.2, coefficient of variation 25.8). Patients taking Slo-bid also had significantly better evening peak flow values than patients taking Theo-Dur (424.5 L/min versus 395.4 L/min). Analysis of other measures of theophylline pharmacokinetics (area under the curve, minimum serum level, occupancy times) as well as diary variables, physical examination findings, and spirometry values showed no differences among the four formulations, although expected individual variability in pharmacokinetics was observed. When Slo-bid was dosed in the evening, higher blood levels were achieved compared with morning administration, suggesting a therapeutic advantage of evening dosing with this product.