To determine whether race and gender affect beta(2)receptor-stimulated bronchodilation, we quantified FEV(1)and plasma concentrations of albuterol at various times following the oral administration of a single 8-mg dose of albuterol in 15 black and 15 white male and female asthmatics. No important racial or gender differences in albuterol-evoked FEV(1)or percent-predicted FEV(1)were evident, although females tended to be more sensitive compared to males. Pharmacodynamic (PD) models were fitted to data in 19 patients (63%); FEV(1)was too erratic to fit in three, and a clockwise hysteresis in the FEV(1)vs. albuterol concentration relationship was observed in eight asthmatics. Mean +/- SD baseline (E(0)), maximal FEV(1)(E(max)) and C(50)were: 3.18 + 1.03 l, 4.00 +/- 1.12 l, 7.84 +/- 10.2 microg/l, respectively. beta(2)receptor genotype was determined in 16 patients. All Arg 16 homozygotes exhibited proportional FEV(1)response vs. plasma albuterol concentration relationships, and thus were fitted by PD models. All those having a poor FEV(1)vs. albuterol concentration relationship carried the Gly 16 allele. We conclude that receptor genotype, but not race or gender, is an important determinant of albuterol pharmacodynamics.
Copyright 2000 Academic Press.