Carvedilol therapy in pediatric patients with congestive heart failure: a study investigating clinical and pharmacokinetic parameters.
OBJECTIVE
Our purpose was to evaluate the clinical effect of carvedilol among pediatric patients with congestive heart failure (CHF) who did not respond to standard therapy and to assess the pharmacokinetics of carvedilol among these children.


METHODS
In this prospective, open intervention trial with blinded interpretation of selected end points, patients with CHF who did not improve on standard therapy, including digoxin, angiotensin-converting enzyme inhibitors, and diuretics, were treated with oral carvedilol in a ramped dosing scheme. Clinical parameters (ejection fraction, fractional shortening, and modified Ross score) were assessed before initiation of treatment and monthly for 6 months. Pharmacokinetic profiles of carvedilol were determined over the first 12-hour period after the initial dose in study patients, and for comparison, in 9 healthy adult volunteers.


RESULTS
Fifteen patients (aged 6 weeks to 19 years) were enrolled in the study, including 10 patients with dilated cardiomyopathy and 5 with CHF secondary to congenital heart disease. All 15 patients tolerated carvedilol for the duration of the trial, and all achieved maximum target dosing. After 6 months of carvedilol therapy, ejection fraction increased (36% vs 54%; P <.05) and modified Ross Score improved (5 +/- 2 vs 3 +/- 3; P <.05). Elimination half-life was about 50% shorter in pediatric CHF patients compared with healthy adult volunteers (2.9 vs 5.2 hours; P <.05).


CONCLUSIONS
Pediatric patients with CHF not responding to standard therapy may benefit from oral carvedilol treatment. The observed increased elimination of carvedilol in children suggests that optimal dosing strategies need to be further defined among the pediatric population.
Läer
Stephanie
S
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Abteilung für Pharmakologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany. laeer@uke.uni-hamburg.de
Mir
Thomas S
TS
Behn
Frederike
F
Eiselt
Michele
M
Scholz
Hasso
H
Venzke
Andrea
A
Meibohm
Bernd
B
Weil
Jochen
J
D000284:Administration, Oral; D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000328:Adult; D002227:Carbazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077261:Carvedilol; D002648:Child; D002675:Child, Preschool; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D018579:Patient Selection; D011412:Propanolamines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011446:Prospective Studies
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol