[Pharmacokinetics and pharmacodynamics of sustained-release theophylline formulation, Slo-bid, in both single and multiple dosing studies of asthmatic children]

Abstract

The pharmacokinetics of theophylline in serum and saliva, and the pulmonary functions were examined in seven asthmatic children aged 9-14 years in both single (6.7 +/- 0.8 micrograms/kg) and multiple dosing settings of sustained-release theophylline formulation, Slo-bid, designed for 12-hour dosing intervals. In the single dose study, the mean maximum concentration (Cmax) and the time taken to reach maximum concentration (Tmax) in serum were 5.5 micrograms/ml and 7.3 hours, and the same parameters in saliva were 3.8 micrograms/ml and 7.3 hours. In the multiple dose study which lasted five days, Cmax, the mean minimum concentration (Cmin), the peak-trough fluctuation (delta P-T) and Tmax in plasma were 13.2 micrograms/ml, 9.9 micrograms/ml, 3.3 micrograms/ml and 5.4 hours, and those in saliva were 10.4 micrograms/ml, 7.0 micrograms/ml, 3.4 micrograms/ml and 5.0 hours, respectively. These results, showing a significant correlation, in both single and multiple dose trials, between the theophylline concentration in serum and the improvement of pulmonary function are support the contention that the therapeutic range of theophylline concentration in serum is 5 to 20 micrograms/ml. There was a significant correlation between the concentration in serum and saliva (r = 0.943, p less than 0.001). The predicted concentrations in serum from those in saliva were +/- 3 micrograms/ml of the measured concentrations in 92.8% of measurements. From these results, we concluded that the sustained-release formulation of theophylline, Slo-bid, is suitable for the treatment in asthmatic children.