Objective: To examine the influence of carvedilol dose and concentration in serum on plasma brain natriuretic peptide (BNP), a measure of heart failure progression.
Methods: 12 patients with New York Heart Association (NYHA) functional class II-III chronic heart failure were enrolled in the study. They received carvedilol at daily doses of 1-20 mg with a 1-2 weekly adjustment. Serum carvedilol trough concentrations were measured in steady-state using a specific fluorescence HPLC method. The degree of improvement in heart failure was assessed from the ratio of change in the plasma BNP concentration, 2 weeks, 1 month and 3 months after the commencement of carvedilol administration.
Results: From the pharmacokinetic aspect, there was no valid correlation between the trough serum carvedilol concentration (Cmin) and daily dose per body weight (Dd/BW), indicating that there was a wide difference in the carvedilol elimination capacity among individuals. A significant decrease in the BNP was observed at the 3rd month in patients treated with the high dose (> 750 mg/3 months). On the other hand, in patients with a mean serum carvedilol level (Cmin) of less than 2.5 nmol/l up to 2 weeks after the start ofcarvedilol therapy, the degree of reduction in the BNP value after the 3rd month was significantly larger, relative to the patient group with Cmin over 2.5 nmol/l.
Conclusions: The total carvedilol dose was confirmed to be one of the determinants for improvement in heart failure, and it was suggested that the initial serum level also plays an important role in therapeutic outcome. Therefore, it may be important to monitor the serum carvedilol level at the introductory period to determine the daily dose requirements because of the wide inter-individual variability in its metabolic clearance.