Impact of genetic polymorphisms of the beta2-adrenergic receptor on albuterol bronchodilator pharmacodynamics.
OBJECTIVE
To determine whether genetic polymorphisms of the beta2-adrenergic receptor gene affect the relationship between albuterol (INN, salbutamol) plasma concentrations and the forced expiratory volume in 1 second (FEV1) in subjects with moderate asthma.


METHODS
Sixteen clinically stable patients with moderate asthma who participated in a pharmacokinetic-pharmacodynamic study of albuterol volunteered to provide a blood sample for determination of beta2-adrenergic receptor genotype. FEV1 and plasma concentrations of albuterol were determined at various times after administration of an oral solution that contained 8 mg albuterol. Patients withheld inhaled beta2-agonist and corticosteroid therapy 12 and 24 hours, respectively, before the study. beta2-Adrenergic receptor genotype was determined by polymerase chain reaction with allele-specific oligonucleotide hybridization.


RESULTS
Albuterol-evoked FEV1 was higher and the response was more rapid in Arg16 homozygotes compared with the cohort of carriers of the Gly16 variant: Maximal percentage increase in FEV1 (%deltaFEV1), 18% versus 4.9% (P < .03); area under FEV1 albuterol concentration curve, 194%.mL/ng versus 30%.mL/ng (P < .05); initial slope (dE/dC), 1.43%.mL/ng versus 0.55%.mL/ng (P < .003).


CONCLUSIONS
The beta2-adrenergic receptor gene polymorphism is a major determinant of bronchodilator response to albuterol. Future pharmacodynamic studies of beta2-agonists should include determination of 02-adrenergic receptor genotype.
Lima
J J
JJ
Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee, Memphis, USA.
Thomason
D B
DB
Mohamed
M H
MH
Eberle
L V
LV
Self
T H
TH
Johnson
J A
JA
D000318:Adrenergic beta-Agonists / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D000420:Albuterol / Q000097:blood / Q000493:pharmacokinetics*; D001120:Arginine / Q000235:genetics; D001249:Asthma / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005541:Forced Expiratory Volume; D005838:Genotype; D005998:Glycine / Q000235:genetics; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012720:Severity of Illness Index
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2; D001120:Arginine; D000420:Albuterol; D005998:Glycine