Pharmacokinetics of R- and S-Carvedilol in Routinely Treated Japanese Patients with Heart Failure

Isao Horiuchi, Takashi Nozawa, Nozomu Fujii, Hiroshi Inoue, Mutsuko Honda, Takako Shimizu, Masato Taguchi, Yukiya Hashimoto
2008 Biological and Pharmaceutical Bulletin  
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 b b-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
more » ... ology of heart failure. In addition, the CL/F values of enantiomers were not correlated with age, creatinine clearance, and plasma concentrations of a a 1 -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.
doi:10.1248/bpb.31.976 pmid:18451529 fatcat:yb5a33mrrvaypj2ijpyphn6yry