Atenolol exposure and risk for development of adverse metabolic effects: a pilot study.

ABSTRACT: To evaluate whether the level of systemic exposure to atenolol explains observed interindividual differences in adverse metabolic responses.Open-label, prospective, pharmacokinetic pilot substudy of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study.General clinical research center.Fifteen hypertensive adults (mean age 46 +/- 8.9 yrs) who were enrolled in the PEAR study.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.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).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.

SUBMITTER: Navare HA 

PROVIDER: S-EPMC2999810 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature