Impact of genetic polymorphisms of the β2-adrenergic receptor on albuterol bronchodilator pharmacodynamics

Objective: To determine whether genetic polymorphisms of the beta(2)-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 beta(2)-adrenergic receptor genotype, FEV1 and plasma concentrations of albuterol were determined at various times aft er administration of an oral solution that contained 8 mg albuterol, Patients withheld inhaled beta(2)-agonist and corticosteroid therapy 12 and 24 hours, respectively, before the study. beta(2)-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 (%Delta FEV1), 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 beta(2)-adrenergic receptor gene polymorphism is a major determinant of bronchodilator response to albuterol, Future pharmacodynamic studies of beta(2)-agonists should include determination of beta(2)-adrenergic receptor genotype.