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

John J. Lima, Donald Thomason, Mohamad H.N. Mohamed, Louis V. Eberle, Timothy H. Self, Julie A. Johnson

Research output: Contribution to journalArticle

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Abstract

Objective: To determine whether genetic polymorphisms of the β2- 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 β2-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 β2-agonist and corticosteroid therapy 12 and 24 hours, respectively, before the study. β2-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 (%ΔFEV1), 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 β2-adrenergic receptor gene polymorphism is a major determinant of bronchodilator response to albuterol. Future pharmacodynamic studies of β2-agonists should include determination of β2-adrenergic receptor genotype.

Original languageEnglish (US)
Pages (from-to)519-525
Number of pages7
JournalClinical Pharmacology and Therapeutics
Volume65
Issue number5
DOIs
StatePublished - May 31 1999

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Albuterol
Bronchodilator Agents
Genetic Polymorphisms
Adrenergic Receptors
Forced Expiratory Volume
Genotype
Asthma
Homozygote
Oligonucleotides
Genes
Oral Administration
Adrenal Cortex Hormones
Pharmacokinetics
Alleles
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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Impact of genetic polymorphisms of the β2-adrenergic receptor on albuterol bronchodilator pharmacodynamics. / Lima, John J.; Thomason, Donald; Mohamed, Mohamad H.N.; Eberle, Louis V.; Self, Timothy H.; Johnson, Julie A.

In: Clinical Pharmacology and Therapeutics, Vol. 65, No. 5, 31.05.1999, p. 519-525.

Research output: Contribution to journalArticle

Lima, John J. ; Thomason, Donald ; Mohamed, Mohamad H.N. ; Eberle, Louis V. ; Self, Timothy H. ; Johnson, Julie A. / Impact of genetic polymorphisms of the β2-adrenergic receptor on albuterol bronchodilator pharmacodynamics. In: Clinical Pharmacology and Therapeutics. 1999 ; Vol. 65, No. 5. pp. 519-525.
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