期刊
BIOLOGICAL & PHARMACEUTICAL BULLETIN
卷 31, 期 5, 页码 976-980出版社
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.31.976
关键词
carvedilol; pharmacokinetics; heart failure; CYP2D6*10
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 (CLIF) of R- and S-carvedilol was not altered by CYP2D6*10, UGT2B7*3, and the etiology of heart failure. In addition, the CLIF values of enantiomers were not correlated with age, creatinine clearance, and plasma concentrations of alpha(1)-acid glycoprotein and brain natriuretic peptide. On the other hand, the mean CLIF values of R- and S-carvedilol in patients with heart failure were 0.89 and 1.52 1/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.
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