Modeling the metabolic effects of terbutaline in beta2-adrenergic receptor diplotypes

Clinical Pharmacology and Therapeutics
John J LimaWilliam J Jusko

Abstract

Our objective was to determine whether beta(2)-adrenergic receptor polymorphisms influence terbutaline-stimulated changes in glucose, insulin, and potassium concentrations in healthy adults. Seven healthy adults homozygous for the Arg-19/Gly16/Glu27 haplotype (RGE) and seven homozygous for the Cys-19/Arg16/Gln27 haplotype (CRQ) volunteered to receive a 1-hour infusion of terbutaline (0.01 mg/kg). A 2-compartment pharmacokinetic model was fitted to the terbutaline concentrations. Concentrations of glucose and insulin were fitted simultaneously by use of a coupled feedback indirect response model. An indirect response model was also fitted to the plasma potassium concentration versus time data. The -2 log-likelihood ratio test was used to determine whether estimates of the covariates of diplotype and sex improved the model fittings. Demographic variables, anthropometric characteristics, and pharmacokinetics did not differ by diplotype. The coupled feedback model fitted the glucose and insulin concentration data well with excellent precision. Terbutaline stimulated production of glucose (S(1)) to a greater extent in RGE compared with CRQ diplotypes, as follows: S(1) = 0.039 +/- 0.007 (mean +/- SD) versus 0.0276 +/- 0.01, respectiv...Continue Reading

Citations

Dec 4, 2010·Journal of Pharmacokinetics and Pharmacodynamics·Wei GaoWilliam J Jusko
Mar 12, 2011·Journal of Pharmacokinetics and Pharmacodynamics·Jing FangWilliam J Jusko
Sep 17, 2011·Journal of Pharmacokinetics and Pharmacodynamics·Jonas B MøllerSteen H Ingwersen
Dec 20, 2011·Pharmaceutical Research·Yanguang CaoWilliam J Jusko
Mar 2, 2012·The Journal of Pharmacology and Experimental Therapeutics·Wei Gao, William J Jusko
May 1, 2008·The AAPS Journal·Johan Gabrielsson, Lambertus A Peletier
Aug 14, 2009·The Journal of Pharmacy Technology : JPT : Official Publication of the Association of Pharmacy Technicians·Orly VardenyKai I Cheang
Nov 13, 2014·Journal of Pharmacokinetics and Pharmacodynamics·Peter GennemarkJohan Gabrielsson
Mar 24, 2012·British Journal of Clinical Pharmacology·Cornelia B LandersdorferWilliam J Jusko
May 3, 2005·Pharmacogenetics and Genomics·Otto-Erich Brodde, Kirsten Leineweber
Mar 29, 2008·Journal of Clinical Pharmacology·Ying HongDonald E Mager
May 26, 2017·Journal of Clinical Pharmacology·Brenda CirincioneDonald E Mager
Mar 31, 2005·Metabolism: Clinical and Experimental·John J LimaJames E Sylvester
Nov 4, 2021·Expert Opinion on Drug Metabolism & Toxicology·Denise TürkThorsten Lehr

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