Dose-related effects of metoprolol on heart rate and pharmacokinetics in heart failure.
BACKGROUND
The pharmacokinetics and pharmacodynamics of immediate-release (IR) metoprolol, 50 mg 3 times daily, were compared with those of different doses of controlled-release/extended-release metoprolol (CR/XL) given once daily.


RESULTS
Fifteen patients with chronic heart failure were randomized to a 3-way crossover study to receive metoprolol IR 50 mg 3 times daily, CR/XL 100 mg once daily, and CR/XL 200 mg once daily for 7 days. On the seventh day of each treatment, serial plasma samples were drawn and standardized exercise tests and a 24-hour Holter recording were performed. Metoprolol IR 50 mg produced peak plasma levels comparable to those observed for CR/XL 200 mg (285 v 263 nmol/L). The difference in mean 24-hour heart rate between CR/XL 100 mg and IR 50 mg was 1.0 bpm (95% confidence interval [CI]), -2.9 to 4.9; NS) compared with -3.8 bpm (95% CI, -7.6 to -0.04; P = .048) between CR/XL 200 mg and IR 50 mg. Submaximal exercise heart rate was lower for patients receiving CR/XL 200 mg than those receiving IR 50 mg. No difference in tolerance or exercise performance was observed between treatment regimens.


CONCLUSIONS
Peak plasma levels produced by metoprolol 200 mg CR/XL were similar to those of 50 mg IR. Metoprolol CR/XL 200 mg was associated with a more pronounced suppression of heart rate than metoprolol IR 50 mg. It is suggested that patients can safely be switched from multiple dosing of metoprolol IR 50 mg to a once-daily dose of metoprolol CR/XL.
Andersson
B
B
Department of Cardiology and Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden.
Aberg
J
J
Lindelöw
B
B
Täng
M S
MS
Wikstrand
J
J
D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015716:Electrocardiography, Ambulatory; D005080:Exercise Test; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008875:Middle Aged
D000319:Adrenergic beta-Antagonists; D008790:Metoprolol