Impact of genetic polymorphisms of the beta(2)-adrenergic receptor on albuterol bronchodilator pharmacodynamics

Objective: To determine whether genetic polymorphisms of the beta(2)-adrene rgic receptor gene affect the relationship between albuterol (INN, salbutam ol) plasma concentrations and the forced expiratory volume in 1 second (FEV 1) in subjects with moderate asthma, Methods: Sixteen clinically stable patients with moderate asthma who partic ipated 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 va rious times aft er administration of an oral solution that contained 8 mg a lbuterol, Patients withheld inhaled beta(2)-agonist and corticosteroid ther apy 12 and 24 hours, respectively, before the study. beta(2)-Adrenergic rec eptor genotype was determined by polymerase chain reaction with allele-spec ific oligonucleotide hybridization, Results: Albuterol-evoked FEV1 was higher and the response was more rapid i n Arg16 homozygotes compared with the cohort of carriers of the Gly16 varia nt: 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 d eterminant of bronchodilator response to albuterol, Future pharmacodynamic studies of beta(2)-agonists should include determination of beta(2)-adrener gic receptor genotype.