Key result
Japanese HF patients show considerably lower carvedilol clearance than healthy subjects.
Why the study?
What are the pharmacokinetics of R- and S-carvedilol in Japanese patients with heart failure?
Observational (n=24)
No
What are the pharmacokinetics of R- and S-carvedilol in Japanese patients with heart failure?
The pharmacokinetics of R- and S-carvedilol are significantly altered by heart failure, resulting in lower oral clearance compared to healthy subjects.
Supports considering reduced carvedilol doses in Japanese heart failure patients; leaves open prospective validation of disease-specific pharmacokinetics.
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.
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Horiuchi et al. (2008) conducted an observational in Heart failure (n=24). Heart failure vs. Healthy subjects (historical) was evaluated on Oral clearance (CL/F) of R- and S-carvedilol. In Japanese patients with heart failure, the mean oral clearance values of R- and S-carvedilol were 0.89 and 1.52 l/h/kg, respectively, which were considerably lower than those previously estimated in healthy subjects.
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