Pharmacokinetics of R- and S-carvedilol in routinely treated Japanese patients with heart failure.
The purpose of this study was to evaluate the pharmacokinetics of R- and S-carvedilol in routinely treated Japanese patients with heart failure. We measured peak and trough blood concentrations at steady state following repeated oral administration to 24 patients. The blood concentration of S-carvedilol with potent beta-blocking activity was lower than that of R-carvedilol. The mean oral clearance (CL/F) of R- and S-carvedilol was not altered by CYP2D6*10, UGT2B7*3, and the etiology of heart failure. In addition, the CL/F values of enantiomers were not correlated with age, creatinine clearance, and plasma concentrations of alpha1-acid glycoprotein and brain natriuretic peptide. On the other hand, the mean CL/F values of R- and S-carvedilol in patients with heart failure were 0.89 and 1.52 l/h/kg, respectively, considerably lower than those estimated previously in healthy subjects. These results suggested that the pharmacokinetics of R- and S-carvedilol was altered significantly by heart failure.
Horiuchi
Isao
I
Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Nozawa
Takashi
T
Fujii
Nozomu
N
Inoue
Hiroshi
H
Honda
Mutsuko
M
Shimizu
Takako
T
Taguchi
Masato
M
Hashimoto
Yukiya
Y
D000319:Adrenergic beta-Antagonists / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D002227:Carbazoles / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077261:Carvedilol; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009961:Orosomucoid / Q000378:metabolism; D011412:Propanolamines / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013237:Stereoisomerism
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D009961:Orosomucoid; D011412:Propanolamines; D000077261:Carvedilol; D019389:Cytochrome P-450 CYP2D6; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase