Cardiovascular effects of timolol maleate, brimonidine or brimonidine/timolol maleate in concomitant therapy.
OBJECTIVE
To examine the influence on maximal exercise performance in young healthy volunteers of timolol 0.5%, brimonidine 0.2% or placebo versus brimonidine 0.2% and timolol 0.5% used concomitantly.


METHODS
The subjects in this prospective, double-masked, crossover comparison were dosed 15 min prior to treadmill testing. A period of 1 week was allowed between tests.


RESULTS
The 20 subjects who completed the trials (average age 24.5 +/- 7.4) had a mean maximum exercise heart rate of 196 +/- 12 bpm for placebo, 182 +/- 13 bpm for timolol, 187 +/- 10 bpm for brimonidine, and 186 +/- 11 bpm for timolol/brimonidine concomitant therapy (p < 0.005). During recovery, the placebo group demonstrated a statistically higher systolic blood pressure (min 6) and pulse (mins 2 and 4) (p < 0.01). In addition, subjects treated with timolol/brimonidine demonstrated more premature contractions (atrial or ventricular) overall during exercise and recovery (p = 0.01). The brimonidine and concomitant treatment groups showed the greatest number of adverse events per subject, the most common of which were dizziness and fatigue (p = 0.031).


CONCLUSIONS
This study suggests that both timolol and brimonidine, used alone and concomitantly, cause cardiovascular effects consistent with their pharmacology.
Stewart
William C
WC
Pharmaceutical Research Corporation, Charleston, South Carolina, USA. pr_admn@bellsouth.net
Stewart
Jeanette A
JA
Jackson
Angi L
AL
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D000068438:Brimonidine Tartrate; D002319:Cardiovascular System / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D015444:Exercise; D005080:Exercise Test; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D011446:Prospective Studies; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology*; D013999:Timolol / Q000008:administration & dosage / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D011810:Quinoxalines; D000068438:Brimonidine Tartrate; D013999:Timolol