Exercise does not affect plasma concentrations of (R)- and (S)-carvedilol.
OBJECTIVE
In vitro studies have shown that beta-blockers are taken up into and released from adrenergic cells. As a consequence, plasma concentrations of beta-blockers increase during exercise together with those of epinephrine and norepinephrine. However, effects of exercise on plasma concentrations of (R)- and (S)-carvedilol are unknown.


METHODS
Twelve healthy males received oral single doses of 12.5 mg (R)-carvedilol, 12.5 mg (S)-carvedilol and 25 mg (R,S)-carvedilol in a cross-over fashion; 11 patients with essential arterial hypertension were given 25 mg (R,S)-carvedilol. Exercise was performed 3 hours following drug intake, and blood samples were taken at rest, at the end of exercise, and after 15 min of recovery. Plasma concentrations of (R)- and (S)-carvedilol were determined by HPLC.


RESULTS
Plasma concentrations of (R)-carvedilol were 2- to 3-fold higher than those of (S)-carvedilol (p < 0.05 in all cases). Plasma concentrations of both (R)- and (S)-carvedilol remained unaffected during exercise and recovery.


CONCLUSIONS
Contrary to all other beta-blockers so far investigated, exercise had no effect on plasma concentrations of (R)- and (S)-carvedilol. We conclude that neither (R)- nor (S)-carvedilol is released from adrenergic cells during exercise, a feature that clearly distinguishes carvedilol from other beta-blockers. Thus, the human organism appears to handle (R)- and (S)-carvedilol differently than other beta-adrenoceptor antagonists. This finding deserves further investigation on a molecular and cellular level in order to clarify these differences between the pharmacokinetics of carvedilol and other beta-blockers.
Stoschitzky
Kurt
K
Division of Cardiology, Karl Franzens University, Graz, Austria. kurt.stoschitzky@uni-graz.at
Koshucharova
Gergana
G
Zweiker
Robert
R
Lercher
Peter
P
Maier
Robert
R
Klein
Werner
W
Zitta
Sabine
S
Gruber
Leonhard
L
Lamprecht
Günther
G
Lindner
Wolfgang
W
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D000328:Adult; D000704:Analysis of Variance; D002227:Carbazoles / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D000077261:Carvedilol; D004311:Double-Blind Method; D015444:Exercise; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D013237:Stereoisomerism
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol