Impact of genetic polymorphisms of the β2‐adrenergic receptor on albuterol bronchodilator pharmacodynamics View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1999-05

AUTHORS

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

ABSTRACT

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. More... »

PAGES

519-525

References to SciGraph publications

  • 1990-04. Clinical Pharmacokinetics of β-Agonists in CLINICAL PHARMACOKINETICS
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1016/s0009-9236(99)70071-8

    DOI

    http://dx.doi.org/10.1016/s0009-9236(99)70071-8

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1013381298

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/10340917


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