Clinical and pharmacokinetic evaluation of a sustained-release liquid theophylline preparation

Theolan Suspension is the first long-acting liquid theophylline dosage form. A crossover study comparing the pharmacokinetic and clinical response to Theolan Suspension (administered every 12 hours) with aminophylline solution (administered every 8 hours) in children younger than 12 years of age is reported. Twenty-seven patients completed the study: 17 children were aged 6 years or younger and five patients were 3 years or younger. All patients were withdrawn from bronchodilator therapy and then were titrated to clinically effective doses of study medication. There was an equivalent and significant reduction from baseline levels in the mean symptom score during administration of theophylline suspension (42%; p less than or equal to 0.001) and aminophylline solution (57%; p less than or equal to 0.001). Mean values for FEV1 (1.2 versus 1.3 L), FEV1/FVC (77% versus 79%), and reduction in acute metaproterenol use (24% versus 43%) in children receiving theophylline suspension and aminophylline solution revealed no differences between products. Adverse effects were reported more frequently for the aminophylline solution, possibly caused in part to its taste. Of children stating a taste preference, eight of 10 children chose the Theolan Suspension. The suspension demonstrated a lower peak theophylline blood level at a later time (11.6 micrograms/ml at 3 1/2 hours), compared to the solution (14.6 micrograms/ml at 1 1/2 hours; p less than or equal to 0.01). Indexes of theophylline fluctuation during the dosing interval indicated equivalent or reduced variability for the suspension. Relative bioavailability of theophylline suspension was 89% of that for the solution.(ABSTRACT TRUNCATED AT 250 WORDS)