Pharmacokinetics of bambuterol during oral administration to asthmatic children

Aims To investigate dose proportionality, dosing frequency, and ethnic aspe cts of the pharmacokinetics of bambuterol in asthmatic children, and to dis cuss the relationship with previous observations in adults. Methods 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) Caucasian s, 12 preschool (2.5 mg vs 5 mg), and 22 school (10 mg vs 20 mg) Orientals. Peak plasma concentrations and dosing interval area under curve (AUC) of b ambuterol and the active metabolite terbutaline were assessed at steady sta te. Treatment differences were analysed statistically within each study. Di fferences between the studies and the relation to steady-state AUC in adult s were described. Results Dose proportionality was seen for terbutaline but not for bambutero l. Twice-daily dosing (2 x AUC(0,12 h)) could not be shown to differ from o nce-daily dosing (AUC(0,24 h)) in the preschool Caucasians. Mean AUC of ter butaline 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 610 nmol l(-1) h in the Oriental school childr en (10 mg; 20 mg). Oriental school children had higher plasma concentration s of bambuterol and terbutaline than Caucasian school children. The strict ethnical implication of the difference could not be elucidated, because dem ographic data were not perfectly matched. Terbutaline AUC was only moderate ly increased in the Caucasian school children compared with Caucasian adult s. The increase was more pronounced in Oriental children and in some presch ool Caucasians. The highest concentration of terbutaline, 58 nmol l(-1) was seen in an Oriental school child after a 20 mg dose. Conclusions Caucasian school children can be given bambuterol hydrochloride very much as Caucasian adults, 10 or 20 mg once daily, but Oriental presch ool and school children plus preschool Caucasians should be given lower dos es.