title: Atenolol exposure and risk for development of adverse metabolic effects: a pilot study.
abstract: OBJECTIVE
  To evaluate whether the level of systemic exposure to atenolol explains observed interindividual differences in adverse metabolic responses.
  
  
  METHODS
  Open-label, prospective, pharmacokinetic pilot substudy of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study.
  
  
  METHODS
  General clinical research center.
  
  
  METHODS
  Fifteen hypertensive adults (mean age 46 +/- 8.9 yrs) who were enrolled in the PEAR study.
  
  
  METHODS
  Patients received atenolol therapy for at least 8 weeks, with 5 of those weeks at a dosage of 100 mg/day, and then underwent a 2-hour oral glucose tolerance test during a pharmacokinetic study visit.
  
  
  RESULTS
  Twenty-hour plasma atenolol concentrations were measured during the pharmacokinetic visit. Glucose and insulin levels were measured during the 2-hour oral glucose tolerance test, and fasting plasma lipid, glucose, and insulin levels were measured at baseline and after 8 weeks of atenolol treatment. A significant association was noted between atenolol area under the concentration-time curve (AUC) and change in fasting glucose level when adjusted for covariates (p=0.0025); the effect was strongest in women. No significant relationship was noted between plasma atenolol concentration and glucose AUC during oral glucose tolerance testing (r=0.08, p=0.78), nor between atenolol AUC and change in triglyceride levels (r=0.13, p=0.63).
  
  
  CONCLUSIONS
  Higher plasma atenolol exposure may be a risk factor for an increase in fasting plasma glucose level during atenolol treatment. These findings require confirmation in a larger sample.
authors.affiliation: Department of Pharmacotherapy and Translational Research, College of Pharmacy, College of Medicine, University of Florida, Gainesville, Florida 32610-0486, USA.
authors.forename: Hrishikesh A
authors.initials: HA
authors.lastname: Navare
authors.forename: Reginald F
authors.initials: RF
authors.lastname: Frye
authors.forename: Rhonda M
authors.initials: RM
authors.lastname: Cooper-Dehoff
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Shuster
authors.forename: Karen
authors.initials: K
authors.lastname: Hall
authors.forename: Siegfried O F
authors.initials: SO
authors.lastname: Schmidt
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Turner
authors.forename: Julie A
authors.initials: JA
authors.lastname: Johnson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D001262:Atenolol / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D001786:Blood Glucose / Q000032:analysis*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D001262:Atenolol
references.citation: Biomed Chromatogr. 2005 Jun;19(5):385-93
references.pmid: 15651086
references.citation: Am Heart J. 2009 Mar;157(3):442-9
references.pmid: 19249413
references.citation: QJM. 2006 Jul;99(7):431-6
references.pmid: 16766516
references.citation: J Hum Hypertens. 2000 Mar;14(3):175-80
references.pmid: 10694831
references.citation: Arch Intern Med. 1999 Mar 22;159(6):551-8
references.pmid: 10090111
references.citation: Reprod Toxicol. 2002 Jan-Feb;16(1):1-7
references.pmid: 11934527
references.citation: Eur J Clin Pharmacol. 1978 May 17;13(2):81-9
references.pmid: 658112
references.citation: Am J Hypertens. 1998 Oct;11(10):1258-65
references.pmid: 9799045
references.citation: JAMA. 2001 May 16;285(19):2486-97
references.pmid: 11368702
references.citation: J Hypertens. 2001 Aug;19(8):1429-35
references.pmid: 11518851
references.citation: J Hypertens. 2007 Jul;25(7):1499-505
references.pmid: 17563574
references.citation: J Cardiovasc Pharmacol. 1993;22 Suppl 6:S87-97
references.pmid: 7508068
references.citation: Clin Pharmacol Ther. 1976 Nov;20(5):524-34
references.pmid: 10125
references.citation: J Hypertens. 1989 Jul;7(7):551-9
references.pmid: 2668407
references.citation: Br Med J. 1979 Jan 13;1(6156):77-80
references.pmid: 761001
references.citation: Cardiovasc Drugs Ther. 1997 Mar;11(1):21-6
references.pmid: 9140673
references.citation: BMJ. 1989 Apr 29;298(6681):1152-7
references.pmid: 2500169
references.citation: JAMA. 2003 May 21;289(19):2560-72
references.pmid: 12748199
references.citation: Br Med J. 1979 Jan 20;1(6157):159-61
references.pmid: 369646
references.citation: Clin Pharmacol Ther. 1979 Apr;25(4):408-15
references.pmid: 428185
references.citation: Acta Physiol Scand Suppl. 1971;372:1-47
references.pmid: 4948309
references.citation: N Engl J Med. 2000 Mar 30;342(13):905-12
references.pmid: 10738048
references.citation: Int J Clin Pharmacol Ther. 2003 Jan;41(1):22-9
references.pmid: 12564742
references.citation: Diabetologia. 1985 Jul;28(7):412-9
references.pmid: 3899825