Bioavailability of a slow-release theophylline capsule given twice daily to preschool children with chronic asthma: comparison with liquid theophylline

The reliability of slow-release theophylline products in young children has been questioned. Therefore, we studied the bioavailability of a commonly prescribed slow-release theophylline formulation (Slo-Bid Gyrocaps), administered twice daily by sprinkling the beads on applesauce. Serial measurements of serum theophylline concentrations were obtained during steady state in eight children (ages 1.6 to 5 years) after receiving a reference liquid theophylline product every six hours and also while receiving the slow-release product every 12 hours. The morning dose of slow-release theophylline was given before the child had eaten, and the evening dose was given two hours after supper. The extent of absorption of the slow-release product was 98.3 +/- 20.2% (mean +/- SD) relative to the liquid reference. The serum concentration fluctuations, expressed as percentage of the measured trough, did not differ between the two products: 108 +/- 59% v 129 +/- 97% (P greater than .05) for reference and slow-release products, respectively. Three of the eight patients had unacceptably large fluctuations (greater than 100%) while receiving the slow-release regimen, and two of these three had unacceptable fluctuations while receiving the liquid reference. The rate of absorption was slower after the evening dose of slow-release product (postprandial), resulting in significantly smaller fluctuations, and lower peak concentrations. Time to peak concentration while receiving the slow-release regimen varied from two to four hours after the evening dose and from two to eight hours after the morning dose. However, the average difference between the peak concentration and the four-hour measurement after the morning dose was only 0.3 microgram/mL (range 0 to 2.6 micrograms/mL).(ABSTRACT TRUNCATED AT 250 WORDS)