Importance of beta(2)adrenergic receptor genotype, gender and race on albuterol-evoked bronchodilation in asthmatics.
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.
Lima
J J
JJ
Department of Clinical Pharmacy, University of Tennessee, Memphis, TN, USA.
Mohamed
M H
MH
Self
T H
TH
Eberle
L V
LV
Johnson
J A
JA
D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000420:Albuterol / Q000097:blood / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D044383:Black People; D001993:Bronchodilator Agents / Q000494:pharmacology*; D005260:Female; D005541:Forced Expiratory Volume; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012737:Sex Factors; D044465:White People
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2; D000420:Albuterol