Pharmacokinetics of bambuterol during oral administration to asthmatic children

To investigate dose proportionality, dosing frequency, and ethnic aspects of the pharmacokinetics of bambuterol in asthmatic children, and to discuss the relationship with previous observations in adults.

Forty-eight children in four different studies completed two double-blind bambuterol treatments each (daily doses of bambuterol hydrochloride): 12 preschool (5 mg x 2 vs 10 mg) and 12 school (10 mg vs 20 mg) Caucasians, 12 preschool (2.5 mg vs 5 mg), and 12 school (10 mg vs 20 mg) Orientals. Peak plasma concentrations and dosing interval area under curve (AUC) of bambuterol and the active metabolite terbutaline were assessed at steady state. Treatment differences were analysed statistically within each study. Differences between the studies and the relation to steady-state AUC in adults were described.

Dose proportionality was seen for terbutaline but not for bambuterol. Twice-daily dosing (2 x AUC(0,12 h)) could not be shown to differ from once-daily dosing (AUC(0,24 h)) in the preschool Caucasians. Mean AUC of terbutaline was 128 and 242 nmol l-1 h in the preschool Caucasians (5 mg/12 h; 10 mg/24 h), 213 and 406 nmol l-1 h in the Caucasian school children (10 mg; 20 mg), 87.4 and 202 nmol l-1 h in the Oriental preschool children (2.5 mg; 5 mg), and 356 and 640 nmol l-1 h in the Oriental school children (10 mg; 20 mg). Oriental school children had higher plasma concentrations of bambuterol and terbutaline than Caucasian school children. The strict ethnic implication of the difference could not be elucidated, because demographic data were not perfectly matched. Terbutaline AUC was only moderately increased in the Caucasian school children compared with Caucasian adults. The increase was more pronounced in Oriental children and in some preschool Caucasians. The highest concentration of terbutaline, 58 nmol l-1, was seen in an Oriental school child after a 20 mg dose.

Caucasian school children can be given bambuterol hydrochloride very much as Caucasian adults, 10 or 20 mg once daily, but Oriental preschool and school children plus preschool Caucasians should be given lower doses.