Impact of genetic polymorphisms of the beta2-adrenergic receptor on albuterol bronchodilator pharmacodynamics

Clin Pharmacol Ther. 1999 May;65(5):519-25. doi: 10.1016/S0009-9236(99)70071-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic beta-Agonists / blood
  • Adrenergic beta-Agonists / pharmacokinetics*
  • Adult
  • Albuterol / blood
  • Albuterol / pharmacokinetics*
  • Arginine / genetics
  • Asthma / blood*
  • Asthma / drug therapy
  • Asthma / physiopathology
  • Bronchodilator Agents / blood
  • Bronchodilator Agents / pharmacokinetics*
  • Female
  • Forced Expiratory Volume
  • Genotype
  • Glycine / genetics
  • Humans
  • Male
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Receptors, Adrenergic, beta-2 / genetics*
  • Severity of Illness Index


  • Adrenergic beta-Agonists
  • Bronchodilator Agents
  • Receptors, Adrenergic, beta-2
  • Arginine
  • Albuterol
  • Glycine