Analysis of Interindividual Variability and Race Difference in the Pharmacokinetics of .BETA.-blocker for Personalized Medicine in Heart Failure Patients

We previously reported that the pharmacokinetics of metoprolol varied greatly among 34 Japanese patients in which the drug was routinely administered due to genetic polymorphisms of CYP2D6 (CYP2D6 *10 ),and that the racial differences in allele frequencies may be responsible for differences in metoprolol therapeutic dose ranges between Caucasians and Japanese.The aim of the present study was to evaluate mechanisms for pharmacokinetic variability of carvedilol and bisoprolol for personalization of β-blocker therapy in Japanese patients with heart failure (HF).The CL /F value of S-carvedilol was decreased in healthy Japanese subjects with CYP2D6 *10 ,although the effect of CYP2D6 *10 was not significant in HF patients.In addition,it was suggested that the activity for CYP2D6 and other carvedilol-metabolizing enzymes was decreased in HF patients.On the other hand,the CL /F value of bisoprolol was decreased in elderly patients.However,pharmacokinetic variability of bisoprolol was small even in routinely treated patients,provided that both body weight and renal function were taken into account for the prediction of CL /F of the drug.These results suggest that bisoprolol is a useful βblocker for the treatment of HF patients.