Atenolol exposure and risk for development of adverse metabolic effects: a pilot study.
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.
Navare
Hrishikesh A
HA
Department of Pharmacotherapy and Translational Research, College of Pharmacy, College of Medicine, University of Florida, Gainesville, Florida 32610-0486, USA.
Frye
Reginald F
RF
Cooper-Dehoff
Rhonda M
RM
Shuster
Jonathan J
JJ
Hall
Karen
K
Schmidt
Siegfried O F
SO
Turner
Stephen T
ST
Johnson
Julie A
JA
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
D000959:Antihypertensive Agents; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D001262:Atenolol
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