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 β-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 α1-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.
2008 The Pharmaceutical Society of Japan