[Pharmacokinetics of theophylline in sustained-release formulation in young asthmatics]

Pharmacokinetics of two theophylline (CAS 58-55-9) sustained release preparations (T: Bronchoretard Capsules/R: Capsule formulation from the US market) were investigated in an open randomised two-way crossover design. The capsules of the test formulation were opened and administered on a tablespoonful of apple sauce. Nineteen asthmatics aged 6 to 12 years participated in this study. Following individual dosing of 100-300 mg theophylline twice a day, a pharmacokinetic profile for 24 h was derived after seven days of multiple dosing. All relevant parameters for rate (Cmax ss, Cmin ss, Cav ss, plateau time, peak-trough fluctuation, nocturnal excess, tmax ss) and extent of absorption (AUCss) were calculated for both formulations. With long plateau times (T: 17.3 h) and small peak-trough fluctuations (T: 49.0%), established quality criteria for high quality theophylline preparations were fulfilled by the test formulation. Furthermore, symmetrical peaks resulted after morning and evening administration of the test formulation. In conclusion, smooth and predictable concentration/time profiles were achieved, enabling an efficacious and safe therapy of asthma. This individual mode of administration allows not only a perfect dose titration in young asthmatics, but is also helpful to patients who have difficulty in swallowing large dosage forms.